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AI Maker Space 38

Postinfarction ventricular septal defect repair: retrospective thoughts and historical perspectives. Evolution of surgical techniques for repair of postinfarction ventricular septal rupture initially involved differentiation of these lesions from prior experience with surgical approaches to congenital ventricular septal defects, which were in the main not applicable. Second, understanding of the differing anatomical locations of postinfarction ventricular septal defects required innovation in terms of the location of the cardiotomy and type of repair necessary to achieve a successful result in any given patient. The gradual appreciation of different clinical courses pursued by patients after postinfarction ventricular septal rupture both in terms of location of the defect and the degree of right ventricular functional impairment has led to increased urgency relative to the timing of surgical repair. The incorporation of specific anatomical concepts of surgical repair and better understanding of the time course of physiological deterioration of patients can ultimately lead to an integrated approach aimed toward improved salvage of patients suffering this catastrophic complication of acute myocardial infarction.

Cardiovascular disease risk profiles. This article presents prediction equations for several cardiovascular disease endpoints, which are based on measurements of several known risk factors. Subjects (n = 5573) were original and offspring subjects in the Framingham Heart Study, aged 30 to 74 years, and initially free of cardiovascular disease. Equations to predict risk for the following were developed: myocardial infarction, coronary heart disease (CHD), death from CHD, stroke, cardiovascular disease, and death from cardiovascular disease. The equations demonstrated the potential importance of controlling multiple risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, glucose intolerance, and left ventricular hypertrophy) as opposed to focusing on one single risk factor. The parametric model used was seen to have several advantages over existing standard regression models. Unlike logistic regression, it can provide predictions for different lengths of time, and probabilities can be expressed in a more straightforward way than the Cox proportional hazards model.

Effects of hepatitis B virus, alcohol drinking, cigarette smoking and familial tendency on hepatocellular carcinoma. Independent and interactive effects related to the development of hepatocellular carcinoma were assessed using a community-based case-control study for hepatitis B virus, habitual alcohol drinking, cigarette smoking, peanut consumption and history of hepatocellular carcinoma among the immediate family. All 200 male newly diagnosed hepatocellular carcinoma patients were recruited consecutively through the period of study as the case group from two teaching medical centers in northern and southern Taiwan. Healthy community residents matched one-to-one with cases on age, sex, ethnic group and residential area were selected as the control group. The carrier status of HBsAg and HBeAg was determined by blind radioimmunoassays, and other risk factors were obtained through standardized interviews according to a structured questionnaire. Conditional logistic regression analysis showed a significant association between hepatocellular carcinoma and the carrier status of HBsAg and HBeAg with an odds ratio of 16.7 and 56.5, respectively, for carriers of HBsAg alone and for carriers of both HBsAg and HBeAg. There was a dose-response relationship between cigarette smoking and hepatocellular carcinoma with an odds ratio of 1.1, 1.5 and 2.6, respectively, for those who smoked 1 to 10, 11 to 20 and more than 20 cigarettes a day. A significant association with hepatocellular carcinoma was also observed for the habitual alcohol consumer with an odds ratio of 3.4. Those whose immediate family had a history of hepatocellular carcinoma were more likely to have the disease develop, with an odds ratio of 4.6. However, the frequency of peanut consumption was not significantly associated with hepatocellular carcinoma.

Leishmania (Viannia) braziliensis: comparative pathology of golden hamsters infected with isolates from cutaneous and mucosal lesions of patients residing in Tres Bracos, Bahia, Brazil. The histopathology of primary forepaw and metastatic lymph node, spleen, and liver lesions produced in golden hamsters infected with cutaneous leishmaniasis (CL) strains (LTB 111 and LTB558) and mucocutaneous leishmaniasis (MCL) strains (LTB12 and LTB201) of Leishmania (Viannia) braziliensis isolated from patients residing in Tres Bracos, Bahia, Brazil is described. No pathological features providing clear differentiation of the CL and MCL strains were found. Although amastigotes were plentiful early in the development of primary forepaw lesions, they were either absent or could not be identified with certainty in sections of late stage lesions. Similarly, amastigotes were not found in histologic lesions at metastatic sites; however, leishmanial DNA was detected in both early and late stage forepaw lesions and metastatic lesions using Leishmania kinetoplast DNA and the gene coding for gp63 as hybridization probes. The DNA recovered from metastatic lesions was extracted from formalin-fixed paraffin-embedded tissues that had been stored at room temperature for prolonged periods.

Visually evoked potentials and electroretinography in neurologic evaluation. Electrophysiologic testing of the visual system requires primarily the ERG and the VEP. The flash electroretinogram provides information about the outer retina only. The pattern electroretinogram is derived from both the outer retina and the innermost retinal layers including the ganglion cell layer. The VEP is based on electrical information recorded from the visual cortex in response to stimulation of the retina. Thus, the integrity of the entire visual pathway can be tested. Localizing ability of the VEP is limited. Since the visual cortex is heavily weighted by representation of the central retina, peripheral lesions, including those producing peripheral visual field abnormalities that do not impinge upon central fixation, may produce relatively little disturbance of the VEP. As with most tests, electrophysiologic studies of the visual system must be placed in context of the entire examination, including the patient's history and neurologic and especially neuro-ophthalmologic evaluation. Electrophysiologic testing has three main uses in neurology. Pattern-reversal VEPs may be useful in detecting hidden visual loss in multiple sclerosis; VEPs and ERGs can distinguish function from organic visual loss; and VEPs and ERGs can be useful in the diagnosis of visual loss in nonverbal patients, especially in children.

Alexia without agraphia associated with spleniogeniculate infarction. Pure alexia, following an infarction in the distribution of the left posterior cerebral artery, is attributed to damage of the left occipital lobe and the splenium of the corpus callosum. We describe a case of pure alexia in a 57-year-old woman with infarction of the left lateral geniculate body and the splenium of the corpus callosum, a variation on this classic disconnection syndrome.

Myasthenia gravis. Myasthenia Gravis is a disorder of neuromuscular function resulting from an immunologically based premature destruction of acetylcholine receptors. The disease is characterized clinically by variable weakness accentuated by repetitive muscular activity and usually responding to the administration of acetylcholinesterase inhibitors. Myasthenia Gravis is a complex disease and requires understanding of the many facets of its natural history and immunological basis to ensure optimal individual patient management. The long-term goal is control of the immunological imbalance; treatment regimens include thymectomy, corticosteroids, azathioprine, and plasmapheresis. The common use of acetylcholinesterase inhibitors provides symptomatic relief during variable daily muscular activity. Disability due to myasthenia gravis is to a large extent reversible and death is preventable. Early recognition of myasthenia gravis and appropriate treatment are often rewarded by remission that may be permanent.

Correction of truncus arteriosus with truncal valvar stenosis or insufficiency using two homografts. Surgical correction of truncus arteriosus requires the creation of right ventricular to pulmonary artery continuity and closure of the ventricular septal defect. A variety of conduits have been used including valved and nonvalved. Despite a significant incidence of truncal valvar stenosis and insufficiency, this valve has seldom been replaced. We present 4 cases of truncus arteriosus with truncal valvar stenosis or insufficiency that were repaired using two valved homografts: one to create the pulmonary outflow tract and the other to replace the abnormal truncal valve. Two of these patients are doing well after 4 months. Another child survived the operation and did well for 2 months when she died suddenly. The last child died 14 hours postoperatively from low cardiac output syndrome secondary to diabetic hypertrophic cardiomyopathy. When truncal valvar abnormalities are present, the primary repair of truncus arteriosus in an infant should include replacement of the truncal valve. Total correction can be successfully achieved using two valved homografts, resulting in long-term palliation and freedom from thromboembolic events and the use of anticoagulants.

The rat glucagon gene is regulated by a protein kinase A-dependent pathway in pancreatic islet cells. A cAMP response element (CRE) has been identified in the proximal 5'-flanking region of the rat glucagon gene, and activation of the cAMP-dependent pathway in fetal rat intestinal cells leads to an increase in the levels of glucagon mRNA transcripts. In contrast, the human glucagon gene does not contain a similar CRE, and the results of studies using immortalized rat and hamster islet cell lines have suggested that glucagon gene expression may not be regulated by cAMP. To reconcile these observations, we have studied the control of glucagon gene expression. Incubation of primary rat islet cell cultures with forskolin in the presence of low (0.5 g/liter) or high (2.0 g/L) glucose resulted in a 2- to 3-fold increase in the levels of glucagon mRNA transcripts. Forskolin also stimulated the secretion and synthesis of immunoreactive glucagon. The importance of the protein kinase-A-dependent pathway in the regulation of glucagon gene expression was also examined in hamster islet InR1-G9 cells. Cotransfection of a glucagon-chloramphenicol acetyltransferase (CAT) fusion gene containing the glucagon CRE and a cDNA encoding the catalytic subunit of protein kinase-A resulted in stimulation of glucagon-CAT activity in hamster islet cells. Catalytic subunit cotransfection also activated somatostatin-CAT, but no activation of RSVCAT was detected. The results of these experiments suggest that the rat glucagon gene is regulated by a protein kinase-A-dependent pathway in the endocrine pancreas.

Reduction in incidence of inducible ventricular tachycardia after myocardial infarction by treatment with streptokinase during infarct evolution. The aim of this study was to determine whether intravenous streptokinase administered with or without oral aspirin to patients with evolving myocardial infarction reduces the inducibility of ventricular tachycardia at electrophysiologic study and thus the risk of sudden death in infarct survivors. Of 159 patients randomized at Westmead Hospital to the multicenter Second International Study of Infarct Survival (ISIS-2) after streptokinase and aspirin in acute myocardial infarction, 87 underwent electrophysiologic testing 6 to 28 days after infarction to determine their risk of subsequent ventricular arrhythmias (streptokinase 20 patients; aspirin 25 patients; streptokinase and aspirin 21 patients; both placebos 21 patients). Patients who underwent electrophysiologic testing had similar clinical characteristics to those of patients who did not. The stimulation protocol comprised up to and including four extrastimuli applied to the right ventricular apex at twice diastolic threshold. An abnormal result was defined as ventricular tachycardia with a cycle length greater than or equal to 230 ms lasting greater than or equal to 10 s. Ventricular tachycardia was inducible at electrophysiologic study in 8 patients who received placebo streptokinase, but in no patient who received active streptokinase (8 of 46 versus 0 of 41; p = 0.005, Fischer's exact test). Ventricular tachycardia was inducible in 4 patients who received aspirin therapy and 4 who did not (4 of 41 versus 4 of 46; p = NS). During a mean follow-up period of 39 +/- 9 months, there were no spontaneous episodes of ventricular tachycardia, ventricular fibrillation or witnessed sudden death in the streptokinase-treated group compared with three such events in the placebo-treated group (p = 0.13). When compared with placebo therapy, intravenous streptokinase substantially reduced the incidence of inducible ventricular tachycardia in infarct survivors. No similar benefit was attributable to aspirin therapy.

Post-traumatic intracerebral pneumatocele: case report. Pneumocephalus occurs in 0.5 to 1.0% of head trauma, but may also occur after neurologic surgery, or as a result of eroding infection or neoplasm. The pathophysiology involves the presence of craniodural fistula allowing ingress of air. A ball-valve mechanism may allow air to enter but not exit the cranium, or CSF leak permits air entrance as fluid leaves the intracranial space. While a "succession splash" is considered diagnostic of pneumocephalus, most patients have nonspecific signs and symptoms such as headache. Therefore, a high index of suspicion in a patient with recent head trauma is necessary. The diagnosis is made radiographically by CT scan. This is generally performed to rule out intracranial hematoma or cerebral contusion in head trauma, but will reveal even very small quantities of air to the unsuspecting physician. Therapy is often noninvasive, allowing the craniodural defect to heal spontaneously. Selected situations require immediate operative repair of the fistula.

Imaging the fetal brain in the second and third trimesters using transvaginal sonography. High-frequency transvaginal probes were used at 20-40 weeks' gestation to develop a systematic examination of the fetal brain. Modeling the procedure after the standard neonatal neurosonographic examination, we attempted to obtain three coronal sections (anterior, midline, posterior) and two sagittal sections (midsagittal, right or left parasagittal). In 70 normal patients, all planes were imaged with a similar frequency (74-76%) except for the posterior coronal plane, which was imaged 59% of the time. Among the first 35 cases, 17% had a complete study, compared with 71% of the second 35 cases. Transvaginal sonography established or changed the diagnosis in five of the 13 cases with central nervous system or other abnormalities. We recommend that a complete fetal neurosonographic examination include transvaginal sonography to complement and enhance the transabdominal examination, especially for cases in which a fetal abnormality is suspected.

Syndromes of transient amnesia: towards a classification. A study of 153 cases. Of 153 patients presenting with acute transient amnesia, 114 fulfilled the proposed strict diagnostic criteria for transient global amnesia (TGA). The prognosis of this group was excellent with the exception of a small subgroup (7%), largely identifiable because of atypically brief or recurrent attacks, who developed epilepsy of temporal lobe type on follow up. Computerised tomography (CT) scans performed on 95 patients were normal, evidence for covert alcoholism was lacking and there was a familial incidence of approximately 2%. By contrast, the group of 39 patients who did not meet the criteria for TGA had a significantly worse prognosis with a high incidence of major vascular events. The groups could not be distinguished on the basis of behavioural characteristics during the attack. The following classification was proposed: 1) pure TGA--attacks fulfilling the strict criteria, and of more than one hour in duration which do not require detailed investigation, 2) probable epileptic amnesia--attacks of less than an hour or rapidly recurrent, 3) probable transient ischaemic amnesia, a minority of cases with additional focal neurological deficits during the attack.

When is a prognostic factor useful? A guide for the perplexed. Traditionally, a number of variables have been used to predict outcome in patients with early-stage breast cancer. These tests are simple to perform and relatively inexpensive. Recently, a number of new factors, eg, tumor proliferative index, nuclear DNA content, and amplification or overexpression of growth-promoting genes or oncogenes have been identified as potential predictors of outcome in patients with breast cancer. There is now increasing pressure to introduce such tests into routine clinical practice. How does a clinical practitioner identify which test, or group of tests, best predicts adverse outcome and whether any more clinically useful information is provided than with the use of more traditional factors alone? The aim of a prognostic test in breast cancer is to predict which patients are destined to develop a recurrence of cancer and those who are not. The prognostic usefulness of a test can be expressed in terms of relative risk (RR), which is the ratio of the risk of breast cancer recurrence in patients who test positive to the risk in those who test negative. Methodologic guidelines that should be satisfied by a study evaluating the predictive ability of a test include the following: (1) Was an inception cohort assembled? (2) Was the referral pattern described? (3) Were laboratory and clinical outcomes assessed in a blinded fashion? (4) Was complete follow-up achieved? (5) Was adjustment for extraneous prognostic factors carried out? (6) Were appropriate statistical methods used? An approach is suggested to help the clinician choose the test, or combination of tests, likely to discriminate between "high-" and "low-risk" patients in his/her own practice. The decision regarding what particular threshold value (risk) defined by a prognostic test (or series of tests) warrants adjuvant therapy for an individual patient is a complex one but should be based on a clear presentation of the risks and benefits to the patient.

Usefulness of d, I sotalol for suppression of chronic ventricular arrhythmias. Sotalol is a unique beta-blocking drug, possessing significant class III antiarrhythmic activity. The efficacy and safety of 2 doses of sotalol (320 and 640 mg/day, divided in 2 doses) were compared to placebo in a 6-week randomized, double-blind, multicenter study of 114 patients with chronic ventricular premature complexes (VPCs) at frequencies of greater than or equal to 30/hour. Sotalol significantly reduced VPCs in patients receiving both low (n = 38) and high (n = 39) doses, compared with patients (n = 37) receiving placebo (by 75 and 88%, respectively, vs 10%; p less than 0.001, sotalol vs placebo; p less than 0.05, high vs low dose). The individual efficacy criterion (greater than or equal to 75% VPC reduction) was achieved in 34% of low-dose and 71% of high-dose sotalol versus 6% of placebo-treated patients (p less than 0.003, sotalol vs placebo; p = 0.007, high vs low dose). Repetitive beats were suppressed 25% by placebo (difference not significant), 80% by low-dose (p less than 0.003) and 78% by high-dose sotalol (p less than 0.005). Sotalol decreased heart rate (by 24 to 25%, p less than 0.001) and increased PR (by 4 to 6%, p less than 0.001) and corrected JT intervals (by 12 to 13%, p less than 0.001), but did not change ejection fraction. Proarrhythmia (nonfatal) occurred in 3 sotalol and in 2 placebo patients. Nine discontinued therapy because of adverse effects (1 low dose and 8 high dose, p less than 0.02). In summary, sotalol is an efficacious antiarrhythmic drug for VPC suppression; in lower doses, it is somewhat less effective but better tolerated.

Endovascular management of arterial intimal defects: an experimental comparison by arteriography, angioscopy, and intravascular ultrasonography. To determine the feasibility of the endovascular management of intimal defects while comparing the accuracy of arteriography with angioscopy and intravascular ultrasonography, we developed an in vivo model of arterial intimal flaps. In 10 superficial femoral arteries of five anesthetized mongrel dogs, intimal flaps were constructed and then imaged by arteriography, angioscopy, and intravascular ultrasound. A flexible microbiopsy forceps was used to remove each intimal flap under angioscopic guidance. Arteriographic lumen diameters were measured and cross-sectional areas calculated. Corresponding measurements by angioscopy and intravascular ultrasound with reduction in luminal area at the flap were obtained by use of computerized planimetry. Uniplanar arteriography identified 60% (6/10) of the intimal flaps, whereas angioscopy and intravascular ultrasound demonstrated 100%. Lumen diameter (in millimeters) measured by arteriography (3.4 +/- 0.6) correlated significantly with measurements by angioscopy (3.5 +/- 0.5, r = 0.77) and intravascular ultrasound (3.5 +/- 0.6, r = 0.96). Similarly, lumen area (square millimeters) by arteriography (9.2 +/- 2.9) correlated with measurements by angioscopy (8.9 +/- 2.2, r = 0.82) and intravascular ultrasound (8.6 +/- 2.7, r = 0.91). Reduction in lumen area by the flap by angioscopy (37 +/- 7%) and intravascular ultrasound (33 +/- 8%) also correlated significantly (r = 0.72). The intimal flaps were removed successfully in all 10 arteries as confirmed by arteriography, angioscopy, and intravascular ultrasound. We conclude that the endovascular management of intimal defects is possible. Additionally, angioscopy and intravascular ultrasound accurately evaluate lumen diameter and area while providing direct assessment of intimal defects.

Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy. Clinical and laboratory characteristics associated with improvement. Of 52 patients fulfilling the criteria of chronic inflammatory demyelinating polyneuropathy, 20 (38%) did not improve after intravenous immunoglobulin treatment, two (4%) had a short-lasting improvement and subsequent infusions had no effect, nine (17%) reached a spontaneously or therapeutically induced complete remission, and 21 patients (40%) needed intermittent infusions to maintain improvement. All patients who improved initially had symptoms that significantly interfered with life-style. After treatment, 90% of these patients were independent in their daily activities. Significantly associated with improvement were disease duration of less than 1 year, progression of weakness until treatment, absence of discrepancy in weakness between arms and legs, areflexia of the arms, and slowed nerve conduction velocity of the motor median nerve. The probability of improvement if all these features are present in 93%.

Precertification for percutaneous transluminal coronary angioplasty in Medicare beneficiaries: a melting pot or a need for better national standards? The Health Care Financing Administration has contracted with state peer review organizations (PROs) in its effort to assure the quality of services and eliminate unreasonable and inappropriate care provided Medicare beneficiaries. By law, each state PRO must select 10 procedures for precertification. Coronary angioplasty has been chosen by 45 PROs for precertification and criteria in each state were developed with the advice of local physicians. This report describes the findings of a survey of these precertification criteria in an effort to determine their variability and to compare the PRO criteria to published national criteria created by expert panels. Current precertification criteria of Medicare beneficiaries show significant variability in the priorities and the clinical practice of cardiologists in performing coronary angioplasty, despite established and published guidelines for its safe and efficacious use. It is likely that the establishment of locally based criteria for coronary angioplasty will be geographically uneven and probably have a less than expected impact on the care provided to Medicare beneficiaries.

Glucose disposal, beta-cell secretion, and hepatic insulin extraction in cirrhosis: a minimal model assessment. Factors controlling glucose metabolism after IV load were studied in nine patients with compensated cirrhosis and in six age-matched controls. The time courses of glucose, insulin, and C peptide were analyzed by means of the minimal model technique. In cirrhosis, insulin sensitivity was reduced by approximately 70% and glucose-dependent glucose uptake (glucose effectiveness) by 45%. Decreased glucose effectiveness explained 65% of the variance of glucose disappearance and correlated with the ratio of urinary creatinine to height, an independent measure of muscle mass (r = 0.839). beta-cell responsiveness to glucose, measured on C-peptide kinetics, was variable and increased on average by 170% and 107% (first-phase and second-phase, respectively). The total amount of insulin secreted by beta-cells in the course of the study was nearly doubled, whereas the basal insulin secretion rate was in the normal range. The time courses of hepatic extraction of insulin did not differ between groups, and basal extraction was on average 58% in controls and 56% in patients with cirrhosis. It was reduced to 30% in a single patient who had severe hepatocellular failure and large spontaneous portosystemic shunting. We conclude that the alterations in glucose metabolism of cirrhosis include a decreased insulin sensitivity, a reduced glucose effectiveness, and an increased pancreatic responsiveness to glucose, leading to hyperinsulinemia. The hepatic extraction of insulin is reduced only in the very advanced stages of the disease, possibly because of a large reserve capacity of the hepatic parenchyma.

A follow-up study of intractable seizures in childhood. One hundred forty-five children with seizures that were refractory to medical therapy for at least 2 years were followed 5 to 20 years after onset. The majority of children with uncontrollable seizures (61%) were mentally retarded, and most of these (73%) had onset of seizures at younger than 2 years of age. Age of onset was significantly later (mean 5.0 +/- 0.5 yr [SEM]) in the group of children with borderline to normal intelligence. Follow-up data showed remission of seizures in a significant proportion of children with borderline or normal intelligence, with a linear decrease of the percentage with persistent seizures at a rate of about 4% per year. Remission of seizures was much less frequent (1.5%/yr) in the group with mental retardation. Seizure type had some effects on outcome. Children with focal atrophic brain lesions did no worse than those without definable pathology on brain-imaging studies.

Thoracoscopic treatment of spontaneous pneumothorax using carbon dioxide laser. In an effort to improve the success rate of the previously described thoracoscopic electrocautery ablation technique of spontaneous pneumothorax, the carbon dioxide laser was evaluated in 12 patients. The recurrent (5 patients) or persistent (7 patients) spontaneous pneumothoraces were caused by rupture of (1) blebs in 6 patients, (2) intrapulmonary apical type II bullae in 3 patients, and (3) diffuse bullous emphysema, type III, in 3. The air leaks were successfully sealed in all but 1 patient with ruptured type II bulla. Surgical specimen from this single failure suggested that the entire inner lining of the bullae must be thermocoagulated. This technical modification led to successful outcome in 2 subsequent cases. With the use of carbon dioxide laser, it was possible to treat not only small blebs but all types of bullae causing spontaneous pneumothorax. Laser thoracoscopy is effective and safe in treating spontaneous pneumothorax.

Surgical treatment of active native valve endocarditis. A report is presented of 24 patients (23 male), mean age 38 years, who underwent surgery for active native valve endocarditis of the left heart in 1975-1988. The aortic valve was affected in all patients, and also the mitral valve in five. Pre-existing aortic valve disorder was present in 17 cases (13 congenitally bicuspid 4 rheumatic affection). There were five hospital deaths (20.8%). Staphylococci as causal organism and extensive infection predicted the highest mortality and morbidity. The mean follow-up time was 39.7 (range 2-114) months. Two reoperations because of prosthetic valve dehiscence revealed endocarditis of the implanted valve. Strong correlation was found between favourable postoperative course and rapid normalization of C-reactive protein levels, which did not fall in patients with persistent infection. Early surgery is recommended if the course of bacterial endocarditis is severely complicated.

Decreased local toxicity with subcutaneous diamorphine (heroin): a preliminary report. We report the cases of 5 patients who developed severe local toxicity during the subcutaneous administration of morphine sulphate and hydromorphone hydrochloride. All patients required site changes more frequently than once every 24 h due to redness, swelling, or pain while receiving morphine or hydromorphone. All patients showed prolongation in the duration of sites of infusion once an equianalgesic dose of diamorphine hydrochloride (heroin) was started. No change in pain control or systemic toxicity was detected with diamorphine. These findings suggest that diamorphine could be a useful alternative for patients who develop severe toxicity to subcutaneous morphine or hydromorphone.

Effect of antiplatelet and anticoagulant therapy on patency of femorotibial bypass grafts. In a retrospective study, 210 autogenous femorotibial saphenous vein grafts inserted during the 15 years from 1967 to 1982 were followed-up for a mean period of 62.3 +/- 5.7 months. Seven patients, who had had eight grafts died in hospital. The remaining 202 grafts fell into three groups: (1) Sixty grafts in patients who received 325 mg of dipyridamole and 1.0 g of acetylsalicylic acid daily, starting on the second postoperative day and continuing for six months. (2) One hundred and two grafts in patients on no antithrombotic therapy. (3) Forty grafts in patients on warfarin therapy to maintain the prothrombin time (prothrombin-proconvertin method) within the therapeutic range (0.10 to 0.20). Medication was continued for six months. This group included more high-risk patients than the other two groups. The mean ages and the incidence of risk factors did not vary significantly between the groups. The patency rates in three groups at five years were 62.5%, 44.0% and 26.0% and at ten years 48.5%, 25.0% and 21.5% for the dipyridamole and acetylsalicylic acid, no therapy and warfarin groups, respectively. The limb salvage rates were 100%, 96% and 85% in the dipyridamole and acetylsalicylic acid, no therapy and warfarin groups respectively. Thus, the best results were seen in the aspirin/dipyridamole group.

Vasopressin and oxytocin responses to illusory self-motion and nausea in man. Vasopressin and oxytocin are nonapeptides secreted from the neurohypophysis; increases in vasopressin are associated with nausea and vomiting in some, but not all, species. Our aim was to determine whether plasma vasopressin and oxytocin levels were altered in healthy volunteers who did or did not develop nausea during vection, an optokinetic stimulus which produces the illusion of self-motion. Vection was produced by rotating a drum with an inner surface of black and white vertical stripes around the seated stationary subject. Gastric myoelectrical activity was recorded continuously throughout the experiment with electrodes positioned on the abdominal surface. Plasma samples were obtained before vection and after drum rotation stopped when nausea and tachygastria were present. Vasopressin and oxytocin were extracted from plasma and quantified by RIA. During vection six subjects reported nausea and developed gastric dysrhythmias; six other subjects had no nausea and remained in normal 3-cpm myoelectrical rhythms. Vasopressin and oxytocin values before vection were similar in each group of subjects. One minute after vection stopped, plasma vasopressin levels were significantly greater (P less than 0.05) in subjects experiencing nausea and tachygastrias (35.4 +/- 26.7 pmol/L) than in those without symptoms (2.7 +/- 0.47 pmol/L). Oxytocin levels were unchanged by either vection or nausea. It is concluded that 1) vasopressin, not oxytocin, neurons in the magnocellular-neurohypophyseal system are activated during vection-induced nausea and gastric dysrhythmias; and 2) illusory self-motion may be used safely to study the neuroendocrine responses to brain-gut interactions and nausea in man.

The recalcitrant perineal wound after rectal extirpation. Applications of muscle flap closure. Perineal wounds developing after abdominoperineal resection result in chronic purulent drainage and intermittent episodes of sepsis and are generally unresponsive to conservative medical and surgical treatment. Thirteen consecutive patients (aged 27 to 74 years; mean, 48 years) who underwent debridement and immediate muscle flap closure of these wounds were analyzed to identify risk factors for delayed healing and to evaluate the effectiveness of muscle flap coverage. Three risk factors were identified: preoperative or postoperative radiation therapy, resection for recurrent carcinoma, and inflammatory bowel disease. A total of 19 muscle flaps (11 gracilis, five gluteal thigh, two gluteus maximus, and one rectus abdominis) were used to close these wounds. During an average 3.5-year follow-up, four (31%) minor complications and one (8%) recurrence were noted to occur. Muscle flaps provide safe, effective, single-stage procedures for the closure of chronic perineal wounds.

Osteotomy for osteoarthritis of the hip. A survivorship analysis. We have reviewed 368 osteotomies carried out for osteoarthritis of the hip at the Nuffield Orthopaedic Centre. Survivorship analysis showed that 10 years after osteotomy 47% had required no further surgery, and even after 20 years 23% had still not had a hip replacement. Hips with moderate arthritic change showed significantly better results than those with more severe degeneration. Osteotomies with varus angulation as well as medial displacement showed longer survival.

In vitro and in vivo evaluation of intraluminal ultrasound in normal and atherosclerotic arteries. This study evaluated the dimensional and morphologic precision of arterial images obtained using intraluminal rotating A-scan ultrasound catheters [5.0F (30 mHz) and 8.0F (20 mHz)]. Dimensions of in vitro ultrasound images from human arteries (eight normal and nine arteriosclerotic) were compared with those from histologic sections of the vessels. In addition, in vivo ultrasound studies (23 normal and 22 arteriosclerotic) of canine femoral arteries were compared with luminal dimensions obtained from angiograms of the vessels. The correlation of in vitro ultrasound images to luminal diameters (n = 22, r = 0.96), adventitial diameters (n = 19, r = 0.83), and wall thickness (n = 19, r = 0.68) in normal human vessels was significant (p less than 0.05). In vitro measurements of images and histologic specimens from human atherosclerotic arteries also correlated significantly (p less than 0.05) with luminal diameters (n = 27, r = 0.91), adventitial diameters (n = 24, r = 0.60), and wall thickness (n = 24, r = 0.62). Morphologically, in vitro images of the wall of normal human arteries had a concentric laminated appearance and atherosclerotic vessels had patchy echodense and echolucent areas. In vivo studies showed significant correlation of diameters for both normal (n = 16, r = 0.91, p less than 0.05) and arteriosclerotic (n = 16, r = 0.57, p less than 0.05) canine arteries compared with luminal dimensions measured from uniplanar angiograms. We conclude that rotating A-scan intraluminal ultrasound accurately defines both normal and atherosclerotic arterial wall morphology and dimensions. This technology may be valuable for intravascular guidance of angioplasty devices by identifying the location and consistency of lesions.

Early outcome after placement of a metallic intracoronary stent: initial Mayo Clinic experience After percutaneous transluminal coronary angioplasty, 3 to 7% of patients have in-hospital coronary closure, and the risk of subsequent myocardial infarction is high, even with an urgent bypass operation. Disrupted coronary morphologic integrity, particularly with large dissections, may be associated with an increased risk of acute coronary closure. A percutaneously placed coronary vascular stent may rapidly alleviate acute or threatened coronary closure and could reduce morbidity. Between October 1989 and June 1990, placement of a balloon-expandable, flexible metallic coil (Gianturco-Roubin) coronary stent was attempted 16 times in 15 Mayo Clinic patients--for treatment of actual or threatened abrupt coronary closure in 10 patients, for primary treatment of a lesion judged to be at high risk for dissection with conventional balloon angioplasty in 1, and for elective treatment of restenotic lesions in 5. Placement of the stent was successful in 15 attempts (94%). Associated complications, which were uncommon, were similar to those noted after balloon angioplasty. No early deaths occurred, and no patient required coronary artery bypass grafting. Stents were successfully placed in both urgent and elective circumstances in native coronary arteries and saphenous vein grafts, and they were used in primary atheromatous and restenotic lesions. Our initial experience with this metallic coil stent indicates that it is efficacious for vascular disruption that is threatening or causing coronary closure after angioplasty. Furthermore, elective placement of a stent may be safely undertaken in patients with high-risk coronary lesions or recurrent restenotic lesions. The long-term outcome in all groups of patients who receive coronary stents is unknown.

Small nodular lesions in the lung periphery: new approach to diagnosis with CT. To evaluate relationships between lesions in the lung periphery and surrounding structures, particularly vessels and bronchi, axial multiplanar reconstruction (AMPR) computed tomography (CT) was used to study 26 patients who underwent surgical resection of pulmonary nodules less than 3 cm in diameter. Findings at AMPR CT, conventional CT, and digital radiographic tomography were compared with findings obtained at evaluation of the resected specimen with regard to the ability to display the relationships between vessels, bronchi, and lesions. AMPR CT was significantly superior to conventional CT and digital radiographic tomography in detecting involvement of pulmonary vessels (P less than .001). Involvement of pulmonary veins was seen in all lung cancers, whereas such involvement was seen in only one of eight nonneoplastic lesions. Thus, involvement of pulmonary veins is strongly suggestive of malignancy. AMPR CT permits three-dimensional visualization and morphologic assessment of pulmonary nodules.

Disturbed gastroduodenal motility in patients with active and healed duodenal ulceration. Disordered gastroduodenal motility may promote duodenal ulceration by allowing prolonged acid contact with the duodenal mucosa. Using a multilumen perfused catheter incorporating 3 pH microelectrodes, antral and duodenal pH and antropyloroduodenal pressure activity were recorded in 36 subjects (10 with healed duodenal ulceration, 11 with active duodenal ulceration, and 15 healthy volunteers) during fasting and after a radiolabeled solid test meal. Correct pH probe/catheter position was continuously verified by recording transmucosal potential difference across the pylorus. Patients with active and healed duodenal ulcer had similarly disordered gastroduodenal motility. The chief abnormalities consisted of an increase in postprandial duodenal retroperistalsis (healed duodenal ulceration, 12 +/- 1 events per hour; active duodenal ulceration, 12 +/- 1; control, 6 +/- 1; mean +/- SEM: healed and active duodenal ulceration vs. control, P = 0.004 and P = 0.03, respectively), a reduction in pressure waves sweeping aborally through the duodenum after the meal (healed duodenal ulceration, 22 +/- 4 events per hour; active duodenal ulceration, 23 +/- 3; control, 34 +/- 4: healed and active duodenal ulceration vs. control, P = 0.04 and P less than 0.05, respectively), and an increased incidence of atypical, complex forms of coordinated duodenal motor activity throughout the study (postprandial data; healed duodenal ulceration, 8 +/- 1 events per hour; active duodenal ulceration, 10 +/- 1; control, 4 +/- 1: healed and active duodenal ulceration vs. control, P = 0.02 and P less than 0.02, respectively). In addition, gastric emptying of the solid test meal was significantly delayed in healed, but not active, duodenal ulceration [half-emptying time, healed duodenal ulceration 185 minutes (117-235); active duodenal ulceration 102 minutes (80-200); control 107 minutes (78-130): healed duodenal ulceration vs. control, P less than 0.009]. Duodenal bulb pH was similar in controls and patients with active duodenal ulceration; however, bulb pH was less than 4 for a significantly greater period of time in healed duodenal ulceration compared with active ulcer patients, particularly after the meal. In conclusion, duodenal ulcer disease is associated with disturbed gastroduodenal motility, even when the ulcer is quiescent and when intraduodenal acidity is low. In healed duodenal ulceration, disturbed motility may promote ulcer relapse by impairing acid clearance from the bulb. However, in active ulceration other factors such as mucosal bicarbonate secretion may have a more influential role in determining intraduodenal pH.

Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma In 20 women with breast carcinoma, 17 of whom had locally advanced cancer and 3 of whom had confirmed metastases, the expression of P-glycoprotein was evaluated before the start of a chemotherapy regimen that included multidrug resistance-related drugs. With the use of the C494 monoclonal antibody in an avidin-biotin-immunoperoxidase technique, P-glycoprotein was detected in 17 of 20 tumor samples. Results were expressed in a semiquantitative manner, taking into account the number of positive tumor cells (N index) and the specific staining intensity (I index). The 17 patients with nonmetastatic cancer were followed from the first cycle of chemotherapy to cancer recurrence; subsequent to six cycles of chemotherapy, all of these patients except one were rendered clinically disease-free through surgery and/or radiation. The end point was defined as either local/regional recurrence or metastasis. Strong P-glycoprotein-positive staining in a majority of tumor cells (the N+/I+ phenotype) was significantly correlated with no initial response to chemotherapy (P less than .02) and with a shorter progression-free survival (P less than .02). Thus, the pretreatment evaluation of P-glycoprotein expression may be of prognostic value in patients with locally advanced breast cancer.

The no-scalpel vasectomy. A refined method of delivering the vas deferens for vasectomy has been developed and used in China since 1974. This method eliminates the scalpel, results in fewer hematomas and infections, and leaves a smaller wound than conventional techniques. An extracutaneous fixation ring clamp encircles and firmly secures the vas without penetrating the skin. A sharp curved hemostat punctures and dilates the scrotal skin and vas sheath. The vas is delivered, cleaned and occluded by the surgeon's preferred technique. The contralateral vas is delivered through the same opening. The puncture wound contracts to about 2 mm., is not visible to the man and requires no sutures for closure. The reported incidence of hematoma in 179,741 men followed in China was 0.09%. No hematomas or infections were identified in the first 273 procedures performed by a surgeon in the United States. The operating time in China and for the last 50 United States procedures has ranged from 5 to 11 minutes. The disadvantage of the technique is the hand-on training and number of cases necessary to gain proficiency. However, the advantages for surgeons and patients should enhance the popularity of vasectomy.

Transcardiac release of leukotriene C4 by neutrophils in patients with coronary artery disease. Leukotriene C4 is a potent constrictor of smooth muscle in vitro and may induce coronary vasoconstriction in vivo. To study leukotriene C4 release by neutrophils in patients with coronary artery disease, neutrophils were separated from blood samples taken from the coronary sinus and aorta in 20 patients with stable exertional angina and angiographically documented coronary artery narrowings (group I). Eight patients with normal coronary arteries were also studied (group II). To assess leukotriene C4 generation, neutrophils were incubated with calcium ionophore A 23187 (0.25 microM) and the supernatants obtained after centrifugation were analyzed for leukotriene C4 by radioimmunoassay. Patients in group I had a significantly lower release of leukotriene C4 from neutrophils separated from the coronary sinus blood than from those separated from aortic blood (4.33 +/- 0.69 versus 5.92 +/- 0.54 ng/ml, p less than 0.025), whereas patients in group II had a similar release of leukotriene C4 by the neutrophils separated from coronary sinus blood and from aortic blood (6.0 +/- 0.72 versus 6.4 +/- 0.66 ng/ml, p = NS). Moreover, in group I patients, a significant correlation was found (p less than 0.01) between the extent of coronary artery disease (expressed by the Leaman coronary score) and the percent reduction in leukotriene C4 released from neutrophils separated from coronary sinus blood as compared with leukotriene C4 produced by neutrophils separated from aortic blood. These data show that neutrophils from patients with coronary artery disease have a reduced ability to produce leukotriene C4 after stimulation by calcium ionophore A 23187.

Comparative study of the effects of three angiotensin converting enzyme inhibitors on the cough reflex. To compare the effects of three different angiotensin converting enzyme (ACE) inhibitors on the cough reflex, capsaicin and citric acid challenge tests were done in normal subjects and hypertensive patients before and after administration of delapril, captopril, or enalapril. Two groups of 7 normal subjects (single dose study: 15 mg delapril v 18.75 mg captopril or 2.5 mg enalapril) and a group of 6 mildly hypertensive patients (1 week study: cross-over administration of 30 mg/day delapril, 37.5 mg/day captopril, or 5 mg/day enalapril) were studied. Another group of 6 patients with essential hypertension was treated with three ACE inhibitors for 4 weeks in a randomized order, with a 2 week washout period between active therapies. Aerosols of 1 mumol/L and 3 mumol/L capsaicin and 0.68% citric acid in 0.9% NaCl were generated by an ultrasonic nebulizer, and the frequency of cough was counted during inhalation. Delapril treatment resulted in substantially fewer patients with a significant increase (greater than or equal to 4 coughs during treatment than during the control period) in the frequency of cough than did captopril treatment. In the 1 and 4 week studies, enalapril and captopril had substantially more occurrences of significantly increased capsaicin-induced cough than did delapril. These results indicate that delapril has the least cough stimulatory effect among these ACE inhibitors, which may be clinically beneficial.

State III squamous cell carcinoma of the vulva. Results of a Swedish study. One hundred fifty-three cases of stage III vulvar squamous cell carcinoma were studied. The survival rate was significantly higher in the 99 patients given standard treatment than in the 54 given other treatments. The principal prognostic factor was the presence of groin metastases. In cases without metastases at the time of primary treatment, the five-year survival rate was 89%; in cases with metastases it was 36% When nodal metastases were not suspected (International Federation of Obstetricians and Gynecologists stage N0N1), the survival rate was also higher than when nodal involvement was suspected (N2). Stage III should be subdivided according to either postoperative stages or new clinical stages by separating N0N1 cases from N2 cases.

Meningeal involvement in Bence Jones multiple myeloma. A case of Bence Jones kappa multiple myeloma with meningeal involvement in a 64-year-old woman is presented. Three years after the diagnosis of multiple myeloma, gait disturbances developed followed by visual disorders and impaired consciousness. A lumbar puncture revealed numerous atypical plasma cells in the cerebrospinal fluid. Craniospinal irradiation and intrathecal injections of methotrexate, cytarabine, and prednisolone were effective for a short period. At autopsy, the leptomeninges were infiltrated diffusely with atypical plasma cells. A review of the literature showed that multiple myeloma with meningeal involvement is accompanied frequently by circulating atypical plasma cells or plasma cell leukemia. Meningeal involvement is a rare complication and shows poor prognosis in cases of multiple myeloma.

CO2 laser for suppurative hidradenitis of the vulva. Chronic suppurative hidradenitis is a disease of the apocrine glands occurring predominantly in the axillae of the anogenital region. Treatment, to date, has been frustrating. Prolonged antibiotic therapy and multiple incisions and drainage have been the usual form of therapy, but those surgical procedures leave patients with ugly scars; retracted, hypertrophic skin edges; and pitted, indurated and disfiguring abscesses. The only successful treatment to date has been wide excision of the entire apocrine gland-bearing tissues, such as radical vulvectomy, which often necessitates grafts to cover the surgically exposed areas. That has left patients with unsatisfactorily functioning vaginas and a mutilated appearance. Recently we instituted the use of the CO2 laser to treat these patients with the goal of eradicating the suppurative sinus tracts and the infected apocrine glands without removing large volumes of adjacent, unaffected tissue. Over the past eight years we treated 11 patients who had extensive, chronic hidradenitis of the anogenital area with the CO2 laser. The use of laser therapy for these patients has produced effective and less-mutilating results. Such treatment has been a successful option for treating this debilitating disease.

Deep femoral lymphadenectomy with preservation of the fascia lata. Preliminary report on 42 invasive vulvar carcinomas. Forty-two patients with primary invasive vulvar carcinoma were treated with radical vulvectomy and deep femoral lymphadenectomy with preservation of the fascia lata and cribriform fascia. The rationale for using this technique was based on anatomic knowledge of the topographic distribution of groin lymph nodes, which was confirmed by the study of 50 cadavers. The preliminary data show that the number of superficial and deep femoral lymph nodes removed from the 42 patients (mean number of nodes, 20; range, 8-32) was similar to the number reported in anatomy books. In addition, the five-year actuarial survival rate, 70%, was comparable to that in the literature. These preliminary results suggest that the surgical technique used in this study is as radical an oncologic procedure as Way's classic groin lymphadenectomy, which consists of removing the fascia lata and cribriform fascia.

Anomalous macular vessels: case report and review of the recent Japanese literature. We examined a 19-year-old woman with large macular vessels who had temporarily impaired visual acuity. The anomalous macular vessels had arteriovenous shunts and were associated with abnormal capillary networks. In a review of the recent Japanese literature, we found another eight patients with anomalous macular vessels who had undergone fluorescein angiography. We prefer the term anomalous macular vessels to describe this condition.

Induced abortions, contraceptive practices, and tobacco smoking as risk factors for ectopic pregnancy in Athens, Greece. A case-control study of the role of induced abortion and other factors on the subsequent occurrence of ectopic pregnancy was undertaken in 1986-1987 in Athens, Greece, where a similar study 20 years ago found a tenfold risk of ectopic pregnancy among women with one or more illegal induced abortions. Seventy women residents of Athens, consecutively admitted to the major state maternity hospital with a diagnosis of ectopic pregnancy, were individually matched with women with a newly diagnosed pregnancy of the same order as the ectopic index pregnancy. Two control women were found for each of 63 cases, but only one control for each of the remaining seven cases. All cases and controls were interviewed by the same qualified obstetrician. Statistical analysis was undertaken with stratification of individual matched triplets and pairs, as well as through conditional multiple regression procedures. The relative risk of recurrence of an ectopic pregnancy was 6.39 with 95% confidence interval (CI) 1.96-21.04. Miscarriages did not increase the risk of ectopic pregnancy. The relative risk for subsequent ectopic pregnancy among women with one or more induced abortion, compared to women without such abortions, was 1.87 (CI 0.84-4.16) controlling only for the matching factors, and 1.71 (CI 0.69-4.27) when marital status (a possible selection factor) was also accounted for in the conditional logistic regression. There was no evidence for increasing risk with increasing number of induced abortions. Past use of an intrauterine device (IUCD) was associated with a relative risk of 3.89 (0.72-21.02); the relative risk increased with the duration of use of the IUCD.

Aneurysmal dilatation in saphenous vein bypass grafts. Three patients are reported who developed aneurysmal degeneration of a saphenous vein arterial bypass graft. All three had hypercholesterolemia and two had marked elevation of triglycerides. One bypass was for occlusive disease and two for popliteal aneurysm. There was a long lag, 3 to 7 years between graft implantation and aneurysmal degeneration. The pathology was similar for all three cases with lipid laden macrophages, loss of elastic lamina, and other atherosclerotic changes in the vein wall. While atheromatous changes and aneurysm formation in saphenous vein bypass grafts are rare, this may occur especially in patients with hypercholesterolemia and hypertriglyceridemia. Careful and prolonged follow-up plus vigorous management of the hyperlipidemic state is mandatory in these patients.

Acute naming deficits following dominant temporal lobectomy: prediction by age at 1st risk for seizures. Age at 1st risk for seizures may predict anomia following dominant anterior temporal lobectomy. We assessed confrontation naming before and 2 to 3 weeks after surgery in 45 right-handed patients grouped by side of focus and presence or absence of early (less than or equal to 5 years) risk factors. After left lobectomy, 6 of 10 (60%) patients with no early risks demonstrated significant decline (greater than or equal to 25%) in naming, but none of the patients with early risks showed this decline. After right lobectomy, there was no change. Cerebral representation of naming may be atypical in patients with early risks.

Surgical outcome in 435 patients who sustained missile head wounds during the Iran-Iraq War. Variables important in predicting the final postsurgical outcome of 435 patients who sustained missile head wounds during the Iran-Iraq War were evaluated over a 99-month period. The type of projectile, site of injury, and presence or absence of foreign material did not seem to have a significant effect on the final outcome. Of the patients with a perforating type of injury, 48.8% had a poor surgical outcome as compared with 19.9% with a penetrating type and 15.6% with a tangential type. This difference is statistically significant (chi 2 = 14.7 and 17.1, respectively; p less than 0.001). The most important factor in predicting overall outcome was the Glasgow Coma Scale (GCS) score at the time of admission. Mortality and morbidity contributing to a poor surgical outcome were noted in only 6% of patients with a GCS score at admission of 13 to 15, in 24.6% of those with a GCS score of 9 to 12, in 57% of those with a GCS score of 6 to 8, and in 65% of those with a GCS score of 3 to 5. Of the 71 patients who died, 75% had a score of 3 to 8. Perforating projectiles or those traversing two or more dural compartments were statistically significant in contributing to mortality and morbidity (chi 2 = 17.2; p less than 0.001). The incidence of focal neurological deficit was 100, 90.6, 88, and 52.2% in patients with GCS scores of 3 to 5, 6 to 8, 9 to 12, and 13 to 15, respectively. The two best predictors of mortality in this group of patients were a low GCS score and infection.

Fine-needle aspiration cytology and flow cytometry of intracystic papillary carcinoma of breast To define criteria for cytologic diagnosis of intracystic papillary carcinoma (ICPC), the authors retrospectively reviewed the fine-needle aspiration (FNA) cytologic specimens of eight cases of histologically proven ICPC of breast. The patients were five black and three white women, 56-87 years of age. The FNA specimen was cyst fluid in four cases (bloody in three, clear in one). All the aspirates showed cellular smears with small and large clusters of cells with papillary and/or cribriform configurations and numerous single epithelial cells. The cells were cuboidal to columnar with minimal atypia. ICPC was suggested by FNA in each case, and all the patients underwent surgical excision or mastectomy. Flow cytometry, performed on fresh FNA specimen in one case and on paraffin-embedded surgical tissue in all eight cases, showed seven tumors to be aneuploid and one to be diploid. The authors contend that ICPCs of breast have distinct cytomorphologic features that can be recognized by FNA. Because ICPC may present in cyst fluid, either bloody or clear, all breast cyst fluids from postmenopausal women should be examined cytologically. Flow cytometric demonstration of an aneuploid population may assist in confirming malignancy in this lesion.

Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. BACKGROUND. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). METHODS. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for factor VIII. The microvessels were carefully counted (per 200x field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. RESULTS. Both microvessel counts and density grades correlated with metastatic disease. The mean (+/- SD) count and grade in the patients with metastases were 101 +/- 49.3 and 2.95 +/- 1.00 vessels, respectively. The corresponding values in the patients without metastases were significantly lower--45 +/- 21.1 and 1.38 +/- 0.82 (P = 0.003 and P less than or equal to 0.001, respectively). For each 10-microvessel increase in the count per 200x field, there was a 1.59-fold increase in the risk of metastasis (95 percent confidence interval, 1.19 to 2.12; P = 0.003). The microvessel count and density grade also correlated with distant metastases. For each 10-microvessel increase in the vessel count per 200x field, there was a 1.17-fold increase in the risk of distant metastasis (95 percent confidence interval, 1.02 to 1.34; P = 0.029). CONCLUSIONS. The number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy.

Hemodynamic consequences of carotid-carotid bypass for innominate artery stenosis. The carotid-carotid cervical bypass is one surgical option for symptomatic atherosclerotic lesions of the innominate artery. Controversy exists regarding the necessity of surgically excluding the innominate plaque from the cerebral circuit. A canine study was instituted to characterize the hemodynamic alterations that occur in the right common carotid artery proximal to the bypass graft, termed the critical segment. The direction of flow in the critical segment determines whether emboli originating in the innominate may be propelled cranially despite a patent bypass graft. Six mongrel dogs underwent placement of an autogenous arterial crossover graft as a carotid-carotid bypass. A stenosis of the innominate artery was quantitatively altered, and an electromagnetic flowmeter measured the magnitude and direction of flow in the critical segment at three levels of diameter reduction in the innominate artery. For low-grade stenoses, flow in the critical segment was always prograde. For high-grade stenoses, the flow was always reversed. Stenoses between 57% and 67% yielded flow values of 10 +/- 24 ml/min, and it was in this range that mean flow reversal was found to occur. Even when the mean flow was near zero in the critical segment, flow was not stagnant but oscillated in antegrade and retrograde directions throughout the cardiac cycle. These data indicate that a carotid-carotid bypass causes complete flow reversal in the critical segment when there is high-grade stenosis in the innominate artery. Theoretical analysis of the hemodynamic circuit indicated that arm exercise would augment retrograde flow in the critical segment.

Gallstone pancreatitis. Choosing and timing treatment. Patients with gallstone pancreatitis are often seen initially by primary care physicians. Prompt diagnosis and timely intervention are crucial in reducing morbidity and mortality. Initial management should include supportive medical care and surgical consultation. The timing of surgery is then dictated by serum enzyme levels and liver function test results as well as by the patient's condition. The role of endoscopic intervention is currently evolving. Whether surgery or endoscopic sphincterotomy is preferable as primary therapy for gallstone pancreatitis remains unresolved. However, sphincterotomy with stone extraction is a viable option in selected cases, especially in patients who have severe gallstone pancreatitis.

Pleuropulmonary manifestations of hepatic amebiasis Pleuropulmonary manifestations of hepatic amebiasis occurred in 30 patients; 18 (60%) presented with at least 1 pulmonary complaint and 10 (33%) had multiple pulmonary symptoms. In 14 patients (47%), abnormalities were found on examination of the chest. In 16 chest roentgenograms (53%), there was at least 1 abnormality: right-sided pleural effusion (9 patients) and elevated right hemidiaphragm (8 patients) were the most common. All patients were treated with metronidazole (Flagyl) and had resolution of the amebic liver abscess and pulmonary disease. Pleuropulmonary disease is a common complication of amebic liver abscess. The clinical presentation and chest roentgenograms are virtually diagnostic and obviate the need for invasive procedures to confirm the diagnosis. Pleuropulmonary disease resolves with amebicidal treatment of the hepatic abscess.

Dissection of the cardinal ligament in radical hysterectomy for cervical cancer with emphasis on the lateral ligament. Surgical experience with carcinomas of the uterus and rectum has provided new insights into the surgical anatomy of a lamina, which separates the paravesical space from the pararectal space. It has been proved that each of the lamina consists of the cardinal and lateral ligaments and pelvic splanchnic nerves, descending in the following order. The cardinal and lateral ligaments, as a connective stalk, insert into the lateral walls of the uterus and rectum extending from the inner aspect of the pelvic wall. Clarification of this structural relationship led to the development of a new procedure for the dissection of the cardinal ligament in radical hysterectomy, while still preserving the lateral ligament. This facilitated systematic dissection of the cardinal and uterosacral ligaments with posterior manipulation, leading to a reduction in blood loss and to prevention of brisk bleeding from the venous plexuses.

Diagnostic echocardiographic features of the sinus venosus defect. To establish the diagnostic criteria for a sinus venosus atrial septal defect cross sectional echocardiograms, cineangiograms, and surgical notes of all patients with this diagnosis seen at the Children's Hospital of Pittsburgh between 1986 and 1988 were reviewed. Seven patients were identified. In each the extent of the atrial septum and the nature of the junction of the superior vena cava with the atria were evaluated echocardiographically from the subcostal position. All had overriding of the superior vena cava and abnormally connected right pulmonary veins. Six patients had undergone cardiac catheterisation and cineangiography. Five patients underwent surgical repair. The operative findings were consistent with the expected morphology in all five, and these features were additionally confirmed in a specimen from the cardiopathological museum. Therefore, the basic anatomical feature of a superior sinus venosus interatrial communication is a biatrial connection of the superior vena cava. This, together with anomalous drainage of the right sided pulmonary veins, results in an interatrial communication outside the confines of the true atrial septum. Overriding of the superior vena cava across the upper rim of the oval fossa is suggested as the pathognomonic diagnostic feature that can clearly be demonstrated echocardiographically from the subcostal position. In essence the lesion is an interatrial communication rather than an atrial septal defect.

Cardiopulmonary perfusion and cerebral blood flow in bilateral carotid artery disease The fear of cerebral complications after cardiopulmonary bypass in patients with heart disease and severe carotid artery disease has led many authors to suggest combined approaches in these patients. The pathogenetic mechanism for stroke is based partly on the stenotic narrowing of the carotid artery. A diameter reduction of 75% is frequently considered hemodynamically significant and indicative of an increased risk for neurological morbidity. We studied the cerebral blood flow in 7 patients undergoing coronary artery bypass grafting who also had severe bilateral carotid disease. The results were compared with the results in 17 patients without carotid disease who had bypass grafting. The cerebral blood flow was measured by xenon 133 washout technique before, during, and after cardiopulmonary bypass with moderate hypothermia. Acid-base regulation was according to the alpha-stat theory, and blood pressure was kept greater than 50 mm Hg. The cerebral blood flow levels (mL.100g-1.min-1) before, during, and after cardiopulmonary bypass in the study group (30 +/- 11, 31 +/- 8, 47 +/- 20) (mean +/- standard deviation) were almost identical to those in the control group (30 +/- 11, 28 +/- 8, 47 +/- 12). The cerebral blood flow levels for the left and right hemispheres in the group with carotid disease were comparable and within normal ranges. In 2 patients, slight differences were noted between hemispheres, and this finding may indicate an increased risk for ischemia. These patients, however, did not show any signs of postoperative deficit. The flow limitations of critical carotid stenoses do not seem to imply a risk for cerebral hypoperfusion if cardiopulmonary perfusion is performed in a controlled manner.

Comparison of omeprazole and cimetidine in reflux oesophagitis: symptomatic, endoscopic, and histological evaluations. Symptomatic patients with endoscopically verified reflux oesophagitis were randomised to a double blind trial in which they received either omeprazole (20 mg once daily) or cimetidine (400 mg four times daily) for four, and if necessary, eight weeks. In an 'intention to treat' analysis, oesophagitis was found to have healed after four weeks in 77 of 137 (56%) in the omeprazole group and in 34 of 133 (26%) in the cimetidine group (p less than 0.001). By eight weeks these values were 71% and 35% respectively; p less than 0.001. Histological assessments were available for 73% of the patients. At entry, 63% (66 of 104) in the omeprazole group and 60% (56 of 94) in the cimetidine group (ns) had abnormal histology. After the study, the proportions of patients who initially had had abnormal histology but who then progressed to normal were 67% (44 of 66: omeprazole) and 48% (27 of 56: cimetidine) respectively (p less than 0.001). All patients had reflux symptoms at entry. After four weeks, 46% in the omeprazole group and 22% (p less than 0.001) in the cimetidine group were asymptomatic. Diary cards completed for the first two weeks showed that patients treated with omeprazole experienced fewer reflux symptoms by day and night and used fewer antacids. Omeprazole, 20 mg once a day for four to eight weeks, healed a greater proportion of patients with reflux oesophagitis than cimetidine, 1.6 g per day, assessed endoscopically and histologically, and relieved more patients' symptoms.

Frequency and significance of occult late potentials on the signal-averaged electrocardiogram in sustained ventricular tachycardia after healing of acute myocardial infarction. The quantitative and morphologic characteristics and significance of late potentials on the signal-averaged electrocardiographic QRS complex remain unknown. To assess this, the signal-averaged electrocardiogram of 48 patients (mean age +/- standard deviation 62 +/- 9 years) with sustained ventricular tachycardia (VT) after healing of acute myocardial infarction and late potentials were analyzed. Late potentials could be classified into 3 morphologic subtypes: type I late potentials (19 patients, 40%) occurred in the terminal 40 ms of the QRS complex; type II late potentials (16 patients, 33%) started before the end of the QRS complex and extended 30 +/- 17 ms into the ST segment; type III late potentials (13 patients, 27%) started after the end of the QRS complex in the ST segment and ended 67 +/- 27 ms after the end of the QRS complex. The amplitude of the late potentials in type III, when compared with types I and II, was significantly lower, whereas the QRS duration on the electrocardiogram in type I, when compared with types II and III, was significantly longer. Computer algorithm based on noise failed to identify most type III late potentials. No difference was noted in age, sex, site of the myocardial infarction, and rate of induced VT among the 3 types.

Hospital admissions from the Surgical Day Care Centre of Vancouver General Hospital 1977-1987. The admissions to Vancouver General Hospital from its Surgical Day Care Centre were reviewed for the period 1977 to 1987. The overall mean rate of admission for the period was 0.28 per cent, for surgically-related admissions 0.22 per cent and for anaesthesia-related admissions 0.07 per cent. The principal reasons for surgery-related admissions were postoperative bleeding, complications, the need for further surgery, the requirement for prolonged postoperative care, and pain. Urology had a particularly high percentage of admissions compared with its workload, because of the diagnostic nature of much of the work. Anaesthesia-related admissions included "syncope," lack of an accompanying adult, aspiration pneumonitis and coincident acute disease. Twelve of the 14 patients admitted with syncope had surgery in the afternoon and had received less than ideal amounts of intravenous fluid. Seven of the 12 ASA physical status II patients admitted had an admission diagnosis related to the coincident disease.

Beneficial effects of x-irradiation on recovery of lesioned mammalian central nervous tissue. We examined the potential of x-irradiation, at clinical dose levels, to manipulate the cellular constituents and thereby change the consequences of transection injury to adult mammalian central nervous tissue (rat olfactory bulb). Irradiation resulted in reduction or elimination of reactive astrocytes at the site of incision provided that it was delivered within a defined time window postinjury. Under conditions optimal for the elimination of gliosis (15-18 days postinjury), irradiation of severed olfactory bulbs averted some of the degenerative consequences of lesion. We observed that irradiation was accompanied by prevention of tissue degeneration around the site of lesion, structural healing with maintenance of the typical cell lamination, and rescue of some axotomized mitral cells (principal bulb neurons). Thus radiation resulted in partial preservation of normal tissue morphology. It is postulated that intrusive cell populations are generated in response to injury and reactive astrocytes are one such group. Our results suggest that selective elimination of these cells by irradiation enabled some of the regenerative processes that are necessary for full recovery to maintain their courses. The cellular targets of these cells, their modes of intervention in recovery, and the potential role of irradiation as a therapeutic modality for injured central nervous system are discussed.

Testicular sex cord stromal tumour with granulosa cell differentiation: detection of steroid hormone receptors as a possible basis for tumour development and therapeutic management. A testicular sex cord stromal tumour with granulosa cell differentiation, typical of granulosa cell tumours of the adult type, was investigated immunohistologically on snap frozen and paraffin wax embedded material. The predominance of vimentin and the additional expression of cytokeratin subtypes 8 and 18, as well as the negative staining for epithelial membrane antigen, accorded with results previously reported, for ovarian granulosa cell tumours; the lack of expression of desmoplakin, however, was a distinctive feature. Together with negative staining for leucocyte common antigen, the antigen pattern facilitates the differential diagnosis between granulosa cell tumour and undifferentiated carcinoma or gonadal lymphoma, although its suitability for differentiating within the group of gonadal stromal tumours seems to be limited. The small growth fraction, shown by the monoclonal antibody Ki-67, is typical of the clinical behaviour of granulosa cell tumours. The expression of oestrogen and progesterone receptors, also recently found in testicular Leydig cell tumours, may provoke new approaches to the management of testicular granulosa cell tumours, as well as a new hypothesis on the development of these tumours.

Interphase cytogenetic analysis in the diagnosis and study of neoplastic disorders. Cytogenetic information usually is obtained through the direct analysis of chromosomes from cells arrested in metaphase. Recently, advances in molecular genetics have made it possible to acquire cytogenetic information through the study of interphase and terminally differentiated cells. By using chromosome-specific DNA probes or probes that are specific for certain chromosomal regions, and by employing techniques of in situ hybridization along with nonradioactive detection methods, it is now possible to detect numerical and structural chromosomal abnormalities from nonmetaphase cells. When used as an adjunct to conventional cytogenetic analysis or when used together with knowledge of established cytogenetic findings for a particular malignancy, this new technology can serve to broaden the scope and utility of cytogenetic analysis beyond the limits of the present metaphase-based technology. Interphase cytogenetic analysis has application to the diagnosis and study of neoplastic disorders and, thus, has particular importance in pathology.

Internal fixation of femoral neck fractures. Two methods compared. In a prospective randomised study, the Hansson pin technique for internal fixation of fractures of the femoral neck was compared with the Uppsala screw technique. The series consisted of 115 consecutive patients, 97 women and 18 men, with a mean age of 80 years. There were 56 patients treated with Hansson pins and 59 with Uppsala screws. After one year 22 patients had died, eight in the Hansson pin group and 14 in the Uppsala screw group (p = 0.28). Twenty-four complications had occurred, 18 in the Hansson pin group and six in the Uppsala screw group (p = 0.008). After exclusion of those with complications, the patients in the Hansson pin group had significantly more pain, less mobility, and a smaller proportion were living in their own homes.

An analysis of outcome following percutaneous transluminal coronary artery angioplasty. An autopsy series. We analyzed autopsy findings on 26 patients who died following percutaneous transluminal coronary angioplasty (PTCA). Twenty-one patients died within 3 weeks of undergoing PTCA; demonstrable cardiac complications were found in 19 patients: platelet-fibrin thrombi (10 patients [48%]), coronary artery dissections (17 patients [81%]), thromboemboli (13 patients [62%]), atheroemboli (seven patients [33%]), and myocardial infarcts (17 patients [81%]). An increased incidence of coronary platelet-fibrin thrombi was noted when compared with a non-PTCA cardiac autopsy population (five of 53 patients). Apparently there was an increased incidence of coronary atheroemboli and thromboemboli in the patients with coronary platelet-fibrin thrombi (eight patients) when compared with patients who did not have platelet-fibrin thrombi (five patients), although this was not statistically significant. There was no evidence of a systemic hypercoagulable state or of disseminated intravascular coagulation. The pathogenesis of this is unclear; however, vasospasm and a disruption of the endothelial surface induced by PTCA with subsequent platelet activation are possible causes. Although not statistically significant, there was a proponderance of female subjects (seven patients) and an increased incidence of diabetes mellitus (six patients) and hypertension (13 patients) when compared with a control population of all patients undergoing PTCA at The Cleveland (Ohio) Clinic Foundation in 1987, suggesting that diabetes mellitus, hypertension, and female sex may be clinical risk factors for fatal complications following PTCA.

Endometriosis associated with massive ascites and absence of pelvic peritoneum. Although massive ascites associated with endometriosis has been reported in rare cases, this patient was also noted to have massive destruction of the pelvic peritoneum. Failure of medical suppression necessitated total abdominal hysterectomy and bilateral salpingo-oophorectomy. Several months after surgery ascites resolved, possibly with reestablishment of the pelvic peritoneum.

Influence of the menstrual cycle on systemic diseases. Physiological changes associated with the menstrual cycle influence the clinical course of some diseases such as bronchial asthma, allergies, anaphylaxis, epilepsy, migraine, dermatoses, and porphyria. Hormonal manipulation can be beneficial in some patients.

Late deaths after treatment for childhood cancer. An investigation of 749 deaths occurring among 4082 patients surviving at least five years after the diagnosis of childhood cancer in Britain before 1971 has been undertaken. Of the 738 with sufficient information the numbers of deaths attributable to the following causes were: recurrent tumour, 550 (74%), a second primary tumour, 61 (8%), a medical condition related to treatment of the tumour, 49 (7%), an traumatic death unrelated to the tumour or its treatment, 34 (5%), finally, any other cause unrelated to the tumour or its treatment, 44 (6%). Less than 10% of five year survivors of non-Hodgkin lymphomas, neuroblastoma, retinoblastoma, Wilms' tumour, or a soft tissue sarcoma died of recurrent tumour during the next 15 years, while more than 25% of five year survivors of Hodgkin's disease, ependymoma, medulloblastoma, and Ewing's tumour died of recurrent tumour during the corresponding period. Almost 50% of five year survivors of acute lymphoblastic leukaemia died of recurrent disease during the corresponding 15 years, a large proportion of deaths being due to central nervous system relapse in an era before central nervous system prophylaxis was routinely given. Comparison of the mortality observed with that expected from mortality rates in the general population indicated three times the expected number of deaths from non-neoplastic causes. Five times the expected number of deaths from cardiovascular causes were observed, these were predominantly myocardial infarction and cerebrovascular accidents. There was no evidence of an excess in the number of suicides observed, but there were three times the expected number of deaths from accidents observed after central nervous system tumours.

Congenital cyst of common bile duct: an unusual cause of obstructive jaundice. Congenital cysts, sometimes referred to as nonparasitic biliary cysts, are not unusual findings in the liver parenchyma, but they have not been previously described in the common bile duct. This clinical report describes a 41-year-old woman with obstructive jaundice that was caused by congenital cysts. The patient had obstruction of the middle portion of the common bile duct; therefore the major differential diagnostic considerations were cholangiocarcinoma, cancer of the pancreas, or true biliary cysts. Congenital cysts, retention cysts, and neoplastic cysts cannot be differentiated from other true cysts preoperatively. Diagnosis can only be established by microscopic examination after surgical excision.

Rapid expression of heat shock protein in the rabbit after brief cardiac ischemia. The effect of brief myocardial ischemia on the expression of heat shock protein (HSP 70) was examined in an in vivo rabbit model of myocardial ischemia using Northern blotting. Functional studies were carried out in the open-chested anesthetized rabbit. The large marginal branch of the left circumflex was occluded four times for 5 min. Using piezoelectric crystals implanted midwall in the ischemic zone, end-diastolic length, end-systolic length, and percent segmental shortening were assessed. Expression of HSP 70 was measured by Northern blotting. A single 5-min coronary occlusion doubled the expression of HSP 70 whereas four cycles of 5 min of ischemia/5 min of reperfusion resulted in a threefold increase in HSP 70 mRNA (P less than 0.001). Measurements with the piezoelectric crystals showed mild myocardial dysfunction concomitant with the increase in HSP 70. This increase in HSP 70 mRNA after repetitive brief ischemia was transient, occurring as early as 1 h and returning to baseline by 24 h after ischemia. Western blot analysis with a monoclonal antibody to HSP 70 was used to compare sham and postischemic myocardial HSP 70 levels. Changes in the amount of HSP 70 were evident as early as 2 h and were even more striking at 24 h.

Relief of tracheal compression by aortopexy. We have performed aortopexy in 12 children with tracheal compression. Six infants had compression secondary to a vascular anomaly (group 1), and the other 6 had previous repair of esophageal atresia (group 2). Eleven of the 12 children are alive after a mean follow-up of 36 months. In group 1, 1 patient died and 3 patients (50%) experienced recurrent respiratory distress. Five infants sustained a major postoperative complication, and the average postoperative hospital stay was 25 days. In group 2, however, aortopexy was uniformly successful. There were no deaths, no postoperative complications, and no cases of postoperative respiratory distress, and the mean postoperative hospital stay was only 10 days. For children with reflex apnea after repair of esophageal atresia, aortopexy is lifesaving and can be performed with minimal morbidity and mortality. Great caution is indicated in children with tracheal compression from other causes.

Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. In this prospective multicenter study, the authors have examined data derived from the initial computerized tomography (CT) scans of 753 patients with severe head injury. When the CT findings were related to abnormal intracranial pressure and to death, the most important characteristics of the scans were: midline shift: compression or obliteration of the mesencephalic cisterns: and the presence of subarachnoid blood. Diffuse hemispheric swelling was also found to be associated with an early episode of either hypoxia or hypotension.

Survey of histologic specimens of human cancer for human papillomavirus types 6/11/16/18 by filter in situ hybridization. Histologic specimens (317) of genital and nongenital cancers and normal tissue were analyzed for the presence of the DNA of human papillomavirus (HPV) 6, 11, 16, and 18 by filter in situ hybridization performed on paraffin-embedded, formalin-fixed tissue (HISTOFISH). HPV DNA was found in 73 of 172 (42%) anogenital lesions and 17 of 116 (15%) nonanogenital carcinomas. No HPV DNA was found in normal mouse skin (five samples), human autopsy liver (two samples), or kidney (eight samples), or in carcinomas of the breast (three samples), bladder (five samples), or colon (nine samples). Of the nongenital tumors, HPV DNA was found in the carcinomas of the lung (2 of 5), anus (7 of 18), esophagus (9 of 39), buccal cavity (1 of 5), and larynx (5 of 50). HPV DNA was also detected in 2 of 11 histologically normal specimens of the cervix and 1 of 3 human skin lesions. The detection of HPV DNA in carcinomas of the lung, larynx, and esophagus as well as in the anogenital region confirms recent suggestions that HPV types 6, 11, 16, and 18 have a wider association with different types of cancer than previously believed. The study also shows that HISTOFISH is a useful method for detecting HPV-DNA in histologic specimens.

Is caffeine withdrawal the mechanism of postoperative headache? This study examined the hypothesis that headache after general anesthesia is related to a caffeine withdrawal state. Two hundred eighty-seven patients undergoing minor elective procedures under general anesthesia were studied. Four to six hours after anesthesia each patient completed a questionnaire assessing his or her own alcohol, tobacco, and caffeine consumption, and the occurrence of postoperative side effects. A highly significant difference was found between the caffeine consumption of patients with and without preoperative (P = 0.0035) and postoperative (P less than 0.0001) headache. Logistic regression analysis of trend between headache and caffeine consumption suggested that with each 100-mg increase in caffeine consumption, there was a 12% increase in the odds of headache developing in the immediate preoperative period (P less than 0.0066) and a 16% increase in the odds of postoperative headache developing (P less than 0.0001). No relationship was found between headache and the patients' age, sex, usual frequency of headache, consumption of alcohol or nicotine, or the anesthetic agents or adjuvants used. It is concluded that postoperative headache is related to caffeine intake and that this relationship is explained, at least in part, by a perioperative caffeine withdrawal syndrome.

Therapy of renal cell carcinoma with interleukin-2 and lymphokine-activated killer cells: phase II experience with a hybrid bolus and continuous infusion interleukin-2 regimen. Forty-seven patients with metastatic or unresectable renal cell carcinoma were treated with interleukin-2 (IL-2) and lymphokine-activated killer (LAK)-cell therapy, using a hybrid IL-2 regimen. IL-2 was administered initially by intravenous bolus (10(5) U/kg [Cetus Corp, Emeryville, CA] every 8 hours for 3 days) during the priming phase, and subsequently by continuous infusion (3 x 10(6) U/m2 for 6 days); during this second treatment period, in vitro-generated LAK cells were administered. Despite selection of patients for good performance status (PS) (29, PS 0; 18, PS 1) prior nephrectomy (43 of the 47 patients), and low tumor burden, the response rate was low (two complete [CRs] and two partial responses [PRs], for an overall objective response rate of 9%). Toxicity was comparable to that experienced with the high-dose bolus regimen. These results suggest that the dose and schedule of IL-2 administration may influence the likelihood of response to IL-2 in renal cell carcinoma.

Intraepithelial anchoring fibril components. Cultured human keratinocytes and cultured human cervical carcinoma cells (ME-180) contained intracellular pools of antigens that reacted with the anchoring fibril antibodies AF1 and AF2. In keratinocytes, these antigens formed a basement membrane-like structure near the apical portions of the cells. Using flow cytometric techniques, pretreatment of the ME-180 cells with acetone revealed large intracellular pools of antigen. The intracellular epitope was calcium sensitive. Some forms of recessive dystrophic epidermolysis bullosa have retention of intracellular portions of the anchoring fibril suggesting a relation of the intracellular anchoring fibril antigens to that disease.

Pulmonary acinar development in diaphragmatic hernia. Pulmonary acinar development was assessed in 17 autopsy cases of pulmonary hypoplasia associated with diaphragmatic hernia. Morphologic examination was conducted by light and electron microscopy, and morphometric study was achieved by radial alveolar count and biochemical quantitation of surfactant phospholipid. In most cases of unilateral diaphragmatic hernia, the ipsilateral lung was underdeveloped morphologically and biochemically compared with the contralateral lung. However, both ipsilateral and contralateral lungs were well developed in some cases of unilateral diaphragmatic hernia. Thus, acinar development of hypoplastic lung in diaphragmatic hernia is varied. The influence of other conditions, such as oligohydramnios, polyhydramnios, and other anomalies that may influence retention of lung fluid or fetal respiratory movement, should be considered to assess the acinar development of hypoplastic lung in diaphragmatic hernia.

Acute autonomic neuropathy. Two cases and a clinical review. Acute autonomic neuropathy is an uncommon syndrome, usually affecting healthy young people. Presentation is often dramatic and initial misdiagnosis is common. We describe two young women with acute autonomic neuropathy who presented with gastrointestinal involvement heralding widespread dysautonomia and review 26 additional cases of acute autonomic neuropathy from the English language literature. Acute autonomic neuropathy can be primarily cholinergic without orthostatic hypotension (26%) or pandysautonomic (74%) involving sympathetic adrenergic functions. Onset has been temporally related to viral syndromes in 20% of cases, with autonomic deficits usually evolving over 1 to 3 weeks. Gastroparesis (69%) and syncope (12%) are frequent presenting complaints. Spinal fluid protein levels are often (75%) elevated in pandysautonomic subtypes. Prolonged and incomplete recovery is the rule (60%), with persistent gastroparesis and orthostatic hypotension. Other specific diseases that occasionally mimic acute autonomic neuropathy include botulism, porphyria, amyloidosis, and paracarcinomatous neuropathies. Acute autonomic neuropathy shares several clinical features with acute idiopathic polyneuropathy (Guillain-Barre syndrome), suggesting an immune-mediated pathogenesis.

Moderate hypothermia after cardiac arrest of 17 minutes in dogs. Effect on cerebral and cardiac outcome. Moderate hypothermia (30 degrees C) induced before circulatory arrest is known to improve neurologic outcome. We explored, for the first time in a reproducible dog outcome model, moderate hypothermia induced during reperfusion after cardiac arrest (resuscitation). In three groups of six dogs each (N = 18), normothermic ventricular fibrillation cardiac arrest (no blood flow) of 17 minutes was reversed by cardiopulmonary bypass--normothermic in control group I (37.5 degrees C) and hypothermic to 3 hours in groups II (32 degrees C) and III (28 degrees C). Defibrillation was achieved in less than or equal to 5 minutes and partial bypass was continued to 4 hours, controlled ventilation to 20 hours, and intensive care to 96 hours. All 18 dogs survived. Electroencephalographic activity returned significantly earlier in groups II and III. Mean +/- SD best neurologic deficit between 48 and 96 hours was 44 +/- 8% in group I, 38 +/- 12% in group II, and 35 +/- 7% in group III (differences not significant). Best overall performance category 2 (good outcome) between 48 and 96 hours was achieved in none of the six dogs in group I and in four of the 12 dogs in the combined hypothermic groups II and III (difference not significant). Mean +/- SD brain total histologic damage score was 130 +/- 22 in group I, 93 +/- 28 in group II (p = 0.05), and 80 +/- 26 in group III (p = 0.03). Gross myocardial damage was greater in groups II and III than in group I--numerically higher overall and significantly higher in group III for the right ventricle alone (p = 0.02). Moderate hypothermia after prolonged cardiac arrest may or may not improve cerebral outcome slightly and can worsen myocardial damage.

Large arteries involvement in scleroderma--a case report. The authors describe a thirty-nine-year-old woman patient presenting with progressive systemic sclerosis and an unusual angiographic picture of an impairment of large arteries, which in their opinion is due to the primary disease. The review literature reports about similar arterial involvement in scleroderma.

Sodium-calcium interactions and salt-sensitive hypertension. In humans with essential hypertension, salt-induced increases in blood pressure have been reported to correlate directly with salt-induced increases in intracellular free calcium [( Ca2+]i) in circulating mononuclear cells. These findings are consistent with the hypothesis that salt-induced increases in [Ca2+]i mediate the phenomenon of salt sensitivity. Circumstantial evidence suggests that salt-induced increases in intracellular sodium or in plasma levels of 1,25-dihydroxy vitamin D might mediate salt-induced increases in [Ca2+]i and blood pressure. However, in humans with salt-sensitive hypertension, it remains to be determined: (1) whether salt-induced increases in white blood cell [Ca2+]i reflect corresponding increases in vascular smooth muscle [Ca2+]i; (2) whether salt-induced increases in [Ca2+]i are a cause or consequence of salt-induced increases in blood pressure; and (3) whether salt-induced increases in 1,25-dihydroxy vitamin D or intracellular sodium precede salt-induced increases in [Ca2+]i.

Effect of stress on diagnosis of hypertension. Blood pressure assessment by a physician elicits an alerting reaction and a pressor response in the patient. The magnitude and time course of this response are described for a large number of hypertensive subjects in whom the assessments were performed during ambulatory intra-arterial blood pressure monitoring. In nearly all of the subjects, the physician's visit was accompanied by blood pressure and heart rate increases that peaked within 4 minutes and then declined. The response was characterized by a relatively high average value; a large between-subject variability; no relation with patient age, baseline hemodynamic values, and responses to laboratory stressors; and no attenuation with multiple repetition of the physician's visit. On the other hand, the increase in blood pressure was considerably less when blood pressure assessment was made by a nurse than when it was made by a physician; in both instances, a 10-minute wait was associated with marked reduction of the initial response. Thus, the stress inherent in usual blood pressure-measuring procedures is responsible for considerable overestimations of patients' blood pressures. There are means by which this can be minimized, although a residual error is likely to remain in most subjects. Whether the stress-devoid blood pressure is a better prognostic index than the stress-related one remains unknown.

Blue breath holding is benign. In their recent publication in this journal, Southall et al described typical cyanotic breath holding spells, both in otherwise healthy children and in those with brainstem lesions and other malformations. Their suggestions regarding possible autonomic disturbances may require further study, but they have adduced no scientific evidence to contradict the accepted view that in the intact child blue breath holding spells are benign. Those families in which an infant suffers an 'apparently life threatening event' deserve immense understanding and help, and it behoves investigators to exercise extreme care and self criticism in the presentation of new knowledge which may bear upon their management and their morale.

T-cell lymphoma and mature nephroblastoma after synchronous bilateral Wilms' tumor. A 15-year-old boy had lymphoblastic lymphoma of the left tonsil after being treated for bilateral Wilms' tumor (BWT) at 7 months of age. In addition, a fully differentiated Wilms' tumor was diagnosed in the remaining, partially nephrectomized left kidney. Development of second malignancies in patients with a history of BWT, as compared with those with unilateral Wilms' tumor, is discussed. A possible explanation for the concurrently diagnosed, fully differentiated Wilms' tumor in the remaining left kidney is suggested.

Sudden infant death syndrome and small airway occlusion: facts and a hypothesis. Respiratory failure is almost certainly the cause of death in the majority of cases of sudden infant death syndrome (SIDS), but the mechanisms leading to it have not been elucidated. SIDS shares many environmental and socioeconomic risk factors with severe forms of bronchiolitis, and the age distribution of incident cases is similar. Present knowledge of lung and airway development during infancy, determinants of peripheral airway patency, changes in lung surface activity in infants with SIDS, and fluid film dynamics in small airways are reviewed. It is hypothesized that many cases of SIDS may be due to a final episode of progressive peripheral bronchial occlusion in infants with preceding critically diminished conductance of the smaller airways.

Otolaryngologic management of patients with subdural empyema. From 1979 to 1988, 17 patients presented to Duke University Medical Center for treatment of subdural empyema. Empyemas were caused by sinusitis in 53% of the patients and by otitis media in 12%. None of those with otologic causes required mastoid drainage, while all patients with sinus infections required sinus drainage. External frontoethmoidectomies were associated with a lower incidence of frontoethmoid re-exploration (P = 0.048), and antrostomies with a lower incidence of maxillary re-exploration (P = 0.111), than were more limited drainage procedures. Sinus drainage performed simultaneously with neurosurgical drainage reduced the incidence of sinus re-exploration (P = 0.167), neurosurgical reexploration (P = 0.048), and length of hospitalization (P = 0.020).

Esophageal adenocarcinoma in a patient with surgically treated achalasia. Although squamous cell carcinoma of the esophagus occurs with increased incidence in primary achalasia, esophageal adenocarcinoma has been considered rare in this condition. We report a patient with long-standing achalasia in whom adenocarcinoma of the esophagus occurred many years after Heller esophagomyotomy, presumably related to Barrett's esophagus complicating gastro-esophageal reflux disease.

Serological arguments for classifying Raynaud's phenomenon as idiopathic. Twenty-five patients with idiopathic Raynaud's phenomenon were followed prospectively for a mean period of 48 months. Clinical and laboratory assessments were performed on admission and on followup. The sera were analyzed for the presence of autoantibodies (antinuclear, antiskeleton and antiorganelle antibodies). Sixteen patients were antinuclear antibody positive and 2 anticentromere antibody positive. Eight patients produced antivimentin, 5 antimitochondrial, 4 anti-Golgi complex, and 3 anticentriol antibodies. Eleven patients produced antidesmosome antibodies. Only one patient (anti-RNP and antidesmosome antibody positive) developed a systemic disease (mixed connective tissue disease) during followup. The initial screening of sera may help to classify Raynaud's phenomenon as idiopathic more accurately.

Management of chronic middle ear effusion with prednisone combined with trimethoprim-sulfamethoxazole. Fifty-three patients were enrolled and evaluable in a randomized, double-blinded controlled clinical trial comparing prednisone for 7 days plus trimethoprim-sulfamethoxazole (TMP/SMZ) for 30 days vs. TMP/SMZ alone in treating chronic middle ear effusion (MEE). Clearing of the effusion in both ears or in one when only one was involved was called complete resolution; clearing in one of two affected ears was called partial resolution. The outcomes 2 weeks after initiation of therapy of 26 patients initially treated with prednisone plus TMP/SMZ were complete resolution in 20, partial resolution in three, and unchanged in three. The outcomes in 27 patients initially treated with TMP/SMZ alone were complete resolution in eight, partial resolution in three, unchanged in 13 and development of acute otitis media in three (P less than 0.01 for complete resolution). Two weeks after initiation of therapy, patients with a MEE that failed to clear were crossed over to the alternative regimen. Overall 29 of 41 patients (71%) who received oral prednisone plus TMP/SMZ initially or after the crossover had complete resolution of their middle ear effusion at 2 weeks after starting prednisone and TMP/SMZ. Five of 35 (14%) patients treated with prednisone plus TMP/SMZ and one of six (17%) patients treated with TMP/SMZ alone who had complete resolution at 4 weeks required subsequent referrals for tympanostomy tubes. A course of prednisone for 7 days plus TMP/SMZ for 30 days with monthly follow-up should be considered in children with MEE persisting beyond 6-8 weeks before referral for tympanostomy tube placement.

Arterial oxygen saturation during induction of anaesthesia Three groups of 10 ASA 1 patients were studied to determine the incidence of hypoxaemia (oxygen saturation less than or equal to 90%) using pulse oximetry during induction of 'mask' anaesthesia, and whether simple oxygenation techniques could prevent its occurrence. We also surveyed all anaesthetists in three major hospitals to ascertain their techniques for this method of anaesthesia. Anaesthesia was induced in all patients with thiopentone and maintained with nitrous oxide and isoflurane. The first group received 33% oxygen in nitrous oxide as carrier gases, a second group a few normal breaths of 100% oxygen during thiopentone administration followed by 33% oxygen in nitrous oxide, while a third group received 100% oxygen after loss of eyelash reflex until spontaneous breathing was established. No patient received positive pressure ventilation before spontaneous breathing was established. Six of the 10 patients in the first group became hypoxaemic compared to none in the second group, and three patients became hypoxaemic in the third group. Thirty-seven percent of anaesthetists who responded to the survey either did not apply positive pressure ventilation before establishment of spontaneous breathing, or only did so if apnoea was prolonged. Only one anaesthetist fully pre-oxygenated patients lungs. We conclude that to avoid the likely occurrence of hypoxaemia during induction of mask anaesthesia, a minimum of a few breaths pre-oxygenation is necessary.

Radiation-induced optic neuropathy: a magnetic resonance imaging study. Optic neuropathy induced by radiation is an infrequent cause of delayed visual loss that may at times be difficult to differentiate from compression of the visual pathways by recurrent neoplasm. The authors describe six patients with this disorder who experienced loss of vision 6 to 36 months after neurological surgery and radiation therapy. Of the six patients in the series, two had a pituitary adenoma and one each had a metastatic melanoma, multiple myeloma, craniopharyngioma, and lymphoepithelioma. Visual acuity in the affected eyes ranged from 20/25 to no light perception. Magnetic resonance (MR) imaging showed sellar and parasellar recurrence of both pituitary adenomas, but the intrinsic lesions of the optic nerves and optic chiasm induced by radiation were enhanced after gadolinium-diethylenetriaminepenta-acetic acid (DTPA) administration and were clearly distinguishable from the suprasellar compression of tumor. Repeated MR imaging showed spontaneous resolution of gadolinium-DTPA enhancement of the optic nerve in a patient who was initially suspected of harboring recurrence of a metastatic malignant melanoma as the cause of visual loss. The authors found the presumptive diagnosis of radiation-induced optic neuropathy facilitated by MR imaging with gadolinium-DTPA. This neuro-imaging procedure may help avert exploratory surgery in some patients with recurrent neoplasm in whom the etiology of visual loss is uncertain.

Functional evaluation of quadriplegic patients using a hand neuroprosthesis. The objective of this retrospective study was to compare the abilities of quadriplegic patients to complete activities of daily living with and without the use of a portable hand neuroprosthesis. The neuroprosthesis provided synthetic hand grasp through functional neuromuscular stimulation of paralyzed forearm and hand muscles. Data were obtained from telephone interviews, patient records, and videotapes. Twenty-two quadriplegic patients were included in the study; 15 were functional at a C5 spinal cord injury level and seven at a C6 level. The median success rate (ie, the percentage of patients who could complete each activity) across the ten activities was 89% with the hand neuroprosthesis but was only 49% without the hand neuroprosthesis. All patients could perform more tasks when the neuroprosthesis was used, although the relative improvement of C5 patients was larger than that of C6 patients.

Circadian rhythms in blood pressure in school-age children of normotensive and hypertensive parents. The purpose of this study was to describe the characteristics of blood pressure rhythms in school-age children and to compare the circadian mesors and amplitudes between children of normotensive parents and children of hypertensive parents. The sample consisted of 40 healthy children between 8 and 10 years old; 20 children had a parental history of hypertension and 20 did not. Blood pressure was measured every 2 hours during the day and every 90 minutes during the night for one 24-hour cycle using a Dinamap monitor equipped with an automatic printer. Cosinor analyses revealed statistically significant circadian rhythms for systolic and diastolic blood pressures in 12 of the 40 subjects. The acrophases for systolic and diastolic pressures occurred between 1200-1800 hours. The mean systolic mesor was 108.50 while the mean diastolic mesor was 61.41. The mean amplitudes were 8.85 for systolic pressure and 7.44 for diastolic pressure. No statistically significant differences in circadian mesors and amplitudes between children of normotensive parents and children of hypertensive parents were found.

Different forms of chronic childhood thrombocytopenic purpura defined by antiplatelet autoantibodies. To determine whether detection of antiplatelet autoantibodies (AAb) to glycoproteins IIb/IIIa and Ib/IX may be useful in defining different forms of chronic thrombocytopenic purpura (TP) in children, we analyzed for AAb the platelet and plasma samples from 36 children with chronic TP (mean duration 4.4 years), from 31 children with normal platelet counts at the time of blood sampling but with chronic TP in the past (mean duration 2.9 years), and from 23 adults with chronic TP; the results were correlated with the clinical data. Antiplatelet autoantibodies were detected in 26 (72.2%) of 36 children with ongoing TP, 15 (48.4%) of 31 children with TP in the past, and 12 (66.7%) of 18 adults with TP. All children with high AAb ratios (greater than 5 times the control mean + 3 SD) were more than 8 years of age at diagnosis (mean age 12.4 years compared with 7.1 years in children with moderate or negative AAb levels; p = 0.003). The results suggest that the outcome for adolescents with high platelet-associated AAb levels may be similar to that of adults, whereas younger children may have a greater chance of spontaneous remission. The children with chronic TP in the past and elevated platelet-associated AAb levels may have a "compensated" TP and therefore may be at risk for relapses. Future studies aimed at serial AAb determination throughout the patients' courses may further define TP subgroups.

Beta-carotene's effects on serum lipoproteins and immunologic indices in humans. Doses of beta-carotene for cancer-prevention trials have been chosen based on epidemiologic data. Mechanisms of the putative antineoplastic effects by beta-carotene are unknown but may involve modulation of the immune system. We measured plasma carotenoid concentrations and selected immunologic indices at baseline and at 2 and 4 wk in 50 healthy humans (5 groups of 10 each) ingesting 0, 15, 45, 180, or 300 mg beta-carotene/d for 1 mo in this randomized placebo-controlled, open-label, parallel study. Plasma beta-carotene concentrations were markedly increased by 2 wk and were correlated with dose. Beta-carotene concentrations plateaued between 2 and 4 wk except for the 300-mg group. Thus, we developed a dose-concentration curve to optimize beta-carotene-dose selection to achieve target plasma concentrations. We were unable to identify any effects of beta-carotene ingestion on the immunologic indices studied, but modest increases in high-density-lipoprotein cholesterol were observed in all beta-carotene-treated groups.

Evolving natural history of coronary artery disease in diabetes mellitus. White diabetic patients are at high risk of developing coronary artery disease (CAD). The natural history of CAD in insulin-dependent (ID) and noninsulin-dependent (NID) diabetes mellitus (DM) is reviewed to gain insight into the mechanisms responsible for the development of premature or accelerated atherosclerosis in diabetic patients. In both IDDM and NIDDM, the risk of CAD increases with lengthening duration of diabetes; the risk, however, does not grow as a constant multiple of the nondiabetic risk of CAD, suggesting that the cumulative exposure to diabetes plays a significant role as a risk factor for CAD only in a subset of patients. This is consistent with the hypothesis that the diabetic milieu has an impact on the progression of atherosclerotic lesions but not on their initiation. This hypothesis is corroborated further by the observation that CAD does not occur in diabetic patients in populations with a low risk of CAD among nondiabetic patients. The component of the diabetic milieu responsible for promotion of atherosclerotic lesions is unknown. There is evidence, however, of a direct or indirect role of hyperinsulinemia in this process.

Iliac versus cranial bone for secondary grafting of residual alveolar clefts. Secondary bone grafting of the maxilla in the mixed transitional dentition stage has become a well-accepted procedure in the surgical protocol for rehabilitation of patients with residual alveolar clefts. This retrospective study was undertaken to evaluate and compare the long-term results obtained with iliac or cranial cancellous bone graft material in the area of alveolar clefts and was based on the independent experience of two plastic surgeons from the same center using exclusively cranial or iliac cancellous bone, respectively. The criteria for surgery were similar. The surgical technique, with the exception of the bone-grafting material, also was similar, and all patients were treated by the same group of orthodontists. Fifteen patients from each group, from a total of over 100 patients, were randomly selected and included in the study. All patients were followed up from 18 to 60 months. Operative and perioperative parameters, donor-site morbidity, and long-term results were evaluated, compared, and analyzed. There were no significant differences between the two groups, and equally good results in terms of bone incorporation, tooth eruption, and appearance were obtained with both iliac and cranial bone grafts. We conclude from our study that successful bone grafting is primarily achieved by adherence to meticulous surgical technique, simultaneous closure of coexisting oronasal or palatal fistulae, use of cancellous bone particles only, and coverage of the grafts with well-vascularized flaps. The source of bone graft does not seem to primarily influence the success of the outcome.

Reviewing the unicystic ameloblastoma: report of two cases. Classification of ameloblastoma into solid, multicystic, unicystic, and peripheral types based on clinical appearance and effects has gained recent recognition. The unicystic ameloblastoma is a less encountered variant of the ameloblastoma. It appears more frequently in the second or third decade with no sexual or racial predilection. It is almost exclusively encountered asymptomatically in the posterior mandible. The following report of two cases discusses the pathophysiology, demographics, histology, and prognosis of the unicystic ameloblastoma.

Chronic calcium channel blockade prevents the progression of myocardial contractile and electrical dysfunction in the cardiomyopathic Syrian hamster. The programmed onset of myocardial dysfunction and its progression to congestive heart failure in the cardiomyopathic Syrian hamster is hallmarked by alterations in myocellular calcium regulation. To determine whether calcium channel blockade is effective in halting the progressive depression of myocardial contractile performance in this animal model of congestive heart failure, oral verapamil therapy was instituted at 50 days of age, and treatment continued for various durations until the time of study at either 150 or 250 days of age. Left ventricular papillary muscle isometric and isotonic performance, as well as transmembrane electrical characteristics, was depressed in diseased hamsters at 150 days of age and deteriorated further by 250 days of age. These changes were evidenced by prolongation of contraction duration, a marked depression in the load-velocity relation, and a significant prolongation in the repolarization phase of the transmembrane action potential. Myocardial functional and electrical alterations associated with the progression of life in myopathic hamsters were completely halted by verapamil therapy that was continuous from 50 days after birth until death by diastolic arrest, at 150 or 250 days of age. However, premature termination of verapamil treatment before death resulted in a progressive renewal of the functional and electrical alterations for the duration of drug termination. It is concluded that the pathological changes seen during the lifetime of the cardiomyopathic hamster can be prevented by continuous calcium channel blockade and that intermediate prevention can be attained by protracted verapamil therapy. Thus, chronic verapamil therapy may be a useful adjunct in the prevention of human congestive heart failure of similar etiology.

A clinicopathological study of the paraneoplastic neuromuscular syndromes associated with lung cancer. The highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma. The clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively. Thirty-five patients had small cell carcinoma and 65 patients non-small cell lung cancer. Clinically, 33 patients had a polymyopathy, of whom 18 had a cachectic myopathy and 15 had a proximal myopathy (two patients had Lambert-Eaton myasthenic syndrome, one presented with dermatomyositis and one had evidence of ectopic ACTH production). Cachexia was more common in non-small cell cancer; proximal myopathy was more common in small cell cancer. Ninety-nine patients had abnormal muscle histology; 74 had type II atrophy, 12 had type I and II atrophy, one had type I atrophy and 12 had necrosis. The majority of patients were affected sub-clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications. Atrophy was not related to the duration of tumour symptoms, ageing, clinical type of myopathy or histological type of lung tumour, and was statistically different from that seen in controls. Qualitatively, the presence of weight loss, muscle wasting and metastatic disease were not factors in the development of atrophy. Similarly, necrosis was not related to the type of lung tumour, the presence of metastases, ageing, weight loss, muscle wasting, duration of tumour symptoms or the clinical form of myopathy. This study demonstrates that lung carcinoma has a direct effect on the motor unit, including atrophy, a necrobiotic myopathy and Lambert-Eaton myasthenic syndrome. Clinical assessment does not accurately assess the 'remote' neuromuscular effects of cancer on the motor unit.

The Merkel cell and associated neoplasms in the eyelids and periocular region. Merkel cells are clear oval cells in the epidermis and outer root sheaths of hair follicles, which are probably of epithelial origin, share ultrastructural features with neuroendocrine cells, and are found in association with touch receptors. In the eyelid, they occur singly in the epidermis and external root sheaths of hairs and eyelashes, and in specialized touch spots alternating with eyelashes. Their typical electron microscopical and antigenic features include dense-core granules, intranuclear rodlets, spinous processes, and a positive reaction for specific cytokeratins, epithelial membrane antigen, neuron-specific enolase, chromogranin and synaptophysin. Merkel cell carcinoma probably develops from precursor cells which give rise to keratinocytes and Merkel cells, and nearly one out of ten Merkel cell carcinomas occur in the eyelid and periocular region. They tend to be bulging lesions near the lid margin of elderly patients, reddish in color, and erythematous with telangiectatic vessels. The diagnosis is based on the frequent presence of neurofilaments and paranuclear aggregates of intermediate filaments in addition to features typical of normal Merkel cells. The tumor often mimics lymphoma or undifferentiated carcinoma and frequently invades lymphatic vessels. One third of Merkel cell carcinomas recur, almost two thirds give rise to regional node metastases, and up to one half metastasize widely and result in death. Initial treatment should be prompt and aggressive, with wide resection and routine postoperative irradiation. Although metastatic lesions often respond to radiation therapy and cytostatic drugs, these treatments are mainly of palliative value.

Chronic musculoskeletal pain and depressive symptoms in the general population. An analysis of the 1st National Health and Nutrition Examination Survey data. Chronic pain and depression frequently occur together. A selection bias afflicts all hospital clinic and family practice populations in which this relationship has been examined. We report here some of the results from civilian populations outside institutions, examined in the United States in national surveys. The findings are based upon the recollection of individuals with respect to the period of 12 months prior to interview and upon the occurrence of depression in the previous week as indicated by the answers to the Depression Scale of the Centre for Epidemiologic Studies (CES-D). They indicate that 14.4% of the United States population between the ages of 25-74 suffer from definite chronic pain related to the joints and musculoskeletal system. Another 7.4% have some pain of uncertain duration. Eighty-three percent of the definite pain group received treatment. Chronic pain subjects scored significantly higher than normals on the CES-D (10.68 +/- S.E.M. 0.76 vs. 8.05 +/- 0.23, P less than 0.01) with subjects with pain of uncertain duration scoring similar to the definite chronic pain population (11.13 +/- 0.76). Using a high cut-off score for depression. 18% of the population with chronic pain were found to have depression. This is in contrast to 8% of the population who did not have chronic pain.

Allograft reconstructions of the shoulder after bone tumor resections. Large skeletal defects resulting from tumor resections about the shoulder create reconstructive challenges for the orthopedic surgeon. Bone allografts offer several advantages compared with other reconstructive techniques, and functional outcomes are generally satisfactory. They may be used either as osteoarticular grafts, intercalated segments to create an arthrodesis, or in combination with standard proximal humerus metallic implants. Patient expectations and specific oncologic factors must be considered when selecting the optimal method of reconstruction.

Oxygen desaturation during fiberoptic bronchoscopy in pediatric patients. STUDY OBJECTIVE: Pulse oximetry was used to measure arterial oxygen saturation and the extent of hypoxemia in pediatric patients undergoing FB. DESIGN: Arterial oxygen saturation was measured (1) prior to the procedure to provide a baseline value, (2) when the bronchoscope was positioned in the nasopharynx, and (3) when the bronchoscope was positioned in the mid-trachea. SETTING: Fiberoptic bronchoscopy was performed in the Pediatric Special Care Unit or in the Pediatric Pulmonary Laboratory using an Olympus BF3C4 fiberoptic bronchoscope with a 3.5-mm outer diameter. PATIENTS OR PARTICIPANTS: Thirty-six children who underwent diagnostic or therapeutic bronchoscopy for a variety of reasons were evaluated. They ranged in age from 6 to 142 months; 20 were male and 16 were female. INTERVENTIONS: There were no interventions. MEASUREMENTS AND RESULTS: Of the 36 patients, 29 experienced a fall in SaO2 levels exceeding 5 percent of baseline values. The youngest age group, 6 to 12 months, showed the greatest drop in saturation as compared with the other groups. Desaturation was significantly increased by midtracheal FB. CONCLUSIONS: A decline in arterial oxygen saturation that may be substantial in infants and children undergoing FB examination was frequently noted, especially in smaller infants and when the bronchoscope was positioned in the mid-trachea. Supplemental oxygen and a brisk procedure time will minimize the risk of dangerous hypoxia.

Duration of the QT interval and total and cardiovascular mortality in healthy persons (The Framingham Heart Study experience). The baseline electrocardiograms of 5,125 original subjects of the Framingham Heart Study were measured to examine the relation of the QT interval corrected for heart rate (QTc) to risk of total mortality, sudden cardiac death, and death due to coronary artery disease over a 30-year follow-up period. Quintiles of QTc (seconds) less than or equal to 0.36, 0.36 to 0.38, 0.39 to 0.40, 0.41 to 0.43 and greater than or equal to 0.44 were studied in relation to these outcomes. There were no significant differences in the risk of total mortality, sudden cardiac death or death due to coronary artery disease according to QTc. A similar lack of significant association between QTc and these 3 outcomes was observed among all persons studied and in the 2 sexes after using a multiple regression analysis to control for several potentially confounding characteristics including age, gender, cigarette smoking, serum total cholesterol, systolic systemic blood pressure and Framingham relative weight. The results of this study fail to demonstrate an association between baseline QTc and overall mortality, and deaths due to sudden cardiac events or coronary artery disease in a large population-based cohort of essentially healthy persons in whom pathologic forms of QTc prolongation are uncommon.