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AI Maker Space 38

Radical intracapsular removal of acoustic neurinomas. Long-term follow-up review of 11 patients. Historically, the neurosurgical treatment of large acoustic neurinomas has developed with two principal goals: complete tumor removal and preservation of facial nerve function. A recent goal for small tumors is the preservation of hearing. Out of a personal series of 124 acoustic neurinomas treated over the past 35 years, the senior author has undertaken a radical intracapsular approach in 12 patients with large tumors (greater than 3 cm in diameter). Surgical indications for intracapsular removal included advanced age (five cases), the patient's wish to avoid any risk of facial paralysis (six cases), contralateral facial palsy (one case), and contralateral deafness (one case). Eleven of these 12 patients were available for follow-up review. Tumor recurrence developed in two patients (18%) at 2 and 3 years postoperatively; there were no late recurrences. Four patients died of unrelated causes, 10 to 19 years after surgery. The remaining five patients have survived a mean of 12 years since surgery without recurrence (range 3 to 22 years). Facial function was preserved in nine patients (82%). The results suggest that radical intracapsular removal may be the procedure of choice under certain circumstances and may offer an alternative to focused high-energy radiation.

Gender differences in Manning criteria in the irritable bowel syndrome. The objective of this study was to determine if gender differences exist when using the Manning criteria for diagnosis of irritable bowel syndrome. In an outpatient setting, 61 women and 36 men with entry complaints of abdominal pain, altered bowel habits, or both underwent full evaluation by board-certified/eligible gastroenterologists who also systematically rated the presence or absence of the six Manning criteria. Irritable bowel syndrome was defined as the absence of an organic disease explanation for the entry complaints. This determination was made by two other board-certified gastroenterologists after patients had been in the study for 9 months. These raters were independent of the study and rated the transcripts of patients' clinic visits, all other available clinical data from this and other clinics, all laboratory data obtained during the 9-month study period, and the results of a 9-month telephone follow-up to patients and their physicians. Sixty-five percent of the study population had no organic disease explanation for the entry symptoms, thereby representing irritable bowel syndrome for this study. A similar proportion and type of organic disease and irritable bowel syndrome were experienced by men and women. For the total sample of 97 subjects, the correlation of the Manning criteria with irritable bowel syndrome was 0.22 (P less than 0.01). In the 61 women, correlation between the Manning criteria and irritable bowel syndrome was significant (r = 0.47; P less than 0.01). In the 36 men, however, the correlation was in the opposite direction, although it was not significant (r = -0.16). It was concluded that significant gender differences exist when using the Manning criteria for the diagnosis of irritable bowel syndrome and that the Manning criteria were not of diagnostic value in men.

Postoperative bile duct strictures. Bile duct strictures are an uncommon but serious complication of primary operations on the gallbladder or biliary tree. Most strictures occur as a result of injury to the bile duct during cholecystectomy. In addition, strictures can occur at the site of previous biliary anastomoses for reconstruction of the biliary tree. Most patients with benign bile duct strictures present soon after their initial operation; however, in some cases, presentation is delayed for years. Cholangiography is essential for defining the anatomy of the biliary tree prior to management. In many cases, nonoperative biliary drainage is useful to treat sepsis and biliary fistulas. A number of alternatives exist for elective repair of bile duct strictures. Experience would suggest, however, that a choledochojejunostomy or hepaticojejunostomy performed through a Roux-en-Y limb of jejunum is the preferable management in most cases. Postoperative biliary stenting may be valuable in optimizing the results. Nonoperative management by percutaneous transhepatic or endoscopic balloon dilatation has been reported to be successful in a number of small series. Long-term results are limited, however. Comparative data suggest that surgical repair for benign postoperative strictures is associated with fewer long-term problems and with similar overall morbidity and costs.

Demonstration of the genuine iso-12p character of the standard marker chromosome of testicular germ cell tumors and identification of further chromosome 12 aberrations by competitive in situ hybridization. The recently developed competitive in situ hybridization (CISH) strategy was applied to the analysis of chromosome 12 aberrations in testicular germ cell tumors (TGCTs). DNAs from two rodent-human somatic cell hybrids, containing either a normal chromosome 12 or the p arm of chromosome 12 as their unique human material, were used as probes. Our results demonstrate a genuine iso-12p character of the standard marker chromosome in TGCTs. Moreover, variant markers were identified representing translocation products that also involve chromosome 12.

Localization of stereotactic targets by microrecordings of thalamic somatosensory evoked potentials. To improve the localization of stereotactic targets, somatosensory evoked potentials (SEPs) were recorded from the thalamus and subthalamic area using a specially designed semimicroelectrode in 61 patients and a conventional "macroelectrode" in 17 patients. By means of the semimicroelectrode, median nerve stimulation evoked two distinct SEPs, consisting of a diphasic wave with a huge positivity restricted to the nucleus ventrocaudalis (Vc) and a triphasic wave of lower amplitude with a major negativity in the ventral part of the nucleus ventrointermedius (Vim) and nucleus ventrooralis posterior (Vop) as well as the subthalamic lemniscal pathway. The Vim-Vc junction could thus be clearly delineated by an abrupt transition of SEPs from one type to the other with a precision of 1 mm. The parvicellular part of the Vc (Vcpc), situated in its basal region, was distinguishable from the Vc proper by a significant reduction of the positivity elicited by stimulation of the median nerve and by a rapid growth of a diphasic SEPs to stimulation of the posterior tibial nerve. In the other thalamic nuclei, stimulation of the median nerve elicited triphasic SEPs of a very small amplitude, suggesting a volume conduction current from the lemniscal pathway. With the macroelectrode, the positivity in the Vc was sensitive to electrode manipulation and the thalamic nuclei could not be distinctly outlined. SEP monitoring using the semimicroelectrode significantly improved the precision of target localization, which allowed minimizing of the volume of the therapeutic lesion without losing surgical effectiveness, while avoiding complications associated with increased penetration of the coagulating electrode. It is suggested that recording serial thalamic SEPs with the semimicroelectrode is a practical method to refine stereotactic targets in the thalamus.

Data compression: effect on diagnostic accuracy in digital chest radiography. High-resolution digital images make up very large data sets that are relatively slow to transmit and expensive to store. Data compression techniques are being developed to address this problem, but significant image deterioration can occur at high compression ratios. In this study, the authors evaluated a form of adaptive block cosine transform coding, a new compression technique that allows considerable compression of digital radiographs with minimal degradation of image quality. To determine the effect of data compression on diagnostic accuracy, observer tests were performed with 60 digitized chest radiographs (2,048 x 2,048 matrix, 1,024 shades of gray) containing subtle examples of pneumothorax, interstitial infiltrate, nodules, and bone lesions. Radiographs with no compression, with 25:1 compression, and with 50:1 compression ratios were presented in randomized order to 12 radiologists. The results suggest that, with this compression scheme, compression ratios as high as 25:1 may be acceptable for primary diagnosis in chest radiology.

A nongastrin malignant ampullary tumor causing gastric acid and pepsin hypersecretion. A case report. We report a case of multiple duodenal ulcers with gastric hypersecretion due to a nongastrin secretagogue produced by a malignant tumor of the pancreas in a 78-year-old man. The case resembled a Zollinger-Ellison syndrome (ZES) with high acid output (basal acid output 27, sham meal-stimulated 37, maximum acid output 47 mEq/h), but with fasting gastrin 43 pg/ml, nonresponsive to secretin. As in ZES, pepsin output was comparatively low, and secretion was inhibitable by atropine (50% inhibited by 1 microM). The tumor removed at surgery contained less than 1 ng gastrin per gram, but was many times more potent than pentagastrin in stimulating acid from a lumen-perfused rat stomach. The tumor also contained cholecystokinin (CCK-8 and CCK-33), motilin, insulin, and somatostatin, which were also present in adjacent normal pancreas; in addition, the tumor contained pancreatic polypeptide and pancreatic cancer-associated antigen. This case represents a rare syndrome due to an as yet undefined peptide secreted by a (frequently malignant) pancreatic endocrine tumor and masquerading as ZES. This is the first report of studies of pepsin secretion and of the effect of atropine, suggesting that the physiologic effects of the secretagogue resemble that of gastrin.

Structural and ultrastructural study of the ovary in childhood leukemia after successful treatment. Ovarian biopsy specimens from ten girls (three postmenarcheal) who had undergone antiblastic treatment for acute lymphoblastic leukemia (ALL) and were in complete remission were examined by light microscope. The biopsy specimens from four of these patients (three postmenarcheal) were also observed by electron microscope. The structural and ultrastructural analysis showed a reduction in the number of follicles which were otherwise normal. No follicles were found in the thin sections from two of the three postmenarcheal girls, whereas normal follicles were observed in the third. The cortical stroma showed moderate to severe signs of fibrosis and changes of capillaries. All of these alterations were more evident in patients where ALL was diagnosed at an older age and this finding suggests that they are at a higher risk for low fertility or early menopause.

Focal nodular hyperplasia of the liver. Twenty-four patients underwent biopsy or resection of the liver for focal nodular hyperplasia (FNH) at Memorial Sloan-Kettering Cancer Center from 1978 to 1988. Twenty-two of the patients were women. The mean age was 35 years. A history of antecedent oral contraceptive or conjugated estrogen (Premarin) use was obtained in 18 of 21 women. There were two men, aged 26 and 37 years; neither gave a history of hormone use. Most of the tumors were solitary (22 of 24) and located in the left lobe of the liver (17 of 22). Fifteen of the patients had a prior or simultaneous malignant lesion and six had other benign tumors. Most of the tumors were resected with a wedge or subsegment of liver (13 of 24). Four patients underwent segmentectomy and five required lobectomy for removal of the tumors. Two patients had an intraoperative biopsy only. The patients in whom the tumor was diagnosed preoperatively underwent computed tomography and arteriography routinely. Scintigraphy of the liver with sulfur colloid was obtained in only three patients, despite its distinct potential for nonoperative diagnosis of FNH.

Clinical management issues in males with sex chromosomal mosaicism and discordant phenotype/sex chromosomal patterns. The recent availability of Y DNA probes has made it possible to identify two forms of 46,XX male syndrome: Y DNA positive and Y DNA negative. The Y DNA positive male results from a X;Y translocation with a low recurrence risk; the Y DNA negative males are due to a mutation with a high recurrence risk. 46,XX males and mosaic forms are phenotypically indistinguishable. A review of the case histories for 11 individuals indicates that affected males have highly variable genital and nongenital phenotypes. Physical findings may be clearly apparent or nonexistent. With the exception of external genitalia, the basis for this variability is unknown. It may be related to differences in Y chromatin expression as the result of variable inactivation of the X chromosomes, or to the existence of minor deletions or point mutations secondary to an exchange of genetic material. Common and uncommon clinical problems in these individuals require evaluation and follow-up care that is provided through a cooperative, interdisciplinary approach.

The lack of full correlation between the Injury Severity Score and the resource needs of injured patients STUDY OBJECTIVE: To determine whether the Injury Severity Score (ISS) correlates with the resource requirements of severely injured patients by studying the association of the ISS with three major interventions (fluid resuscitation, invasive central nervous system monitoring, and acute operative repair) trauma centers routinely provide severely injured patients. DESIGN: Retrospective clinical review. SETTING: Level I trauma center. TYPE OF PARTICIPANTS: Eight hundred fourteen adult injured patients. MEASUREMENTS AND MAIN RESULTS: When an ISS of more than 9 was used as the definition of major trauma, the ISS undercorrelated 11% of the time with the need for any one procedure. When an ISS of more than 14 was used as the definition, it undercorrelated 20% of the time. CONCLUSION: The ISS may not be completely correlated with the resource requirements of injured patients and should not be used as the sole means by which to define major injury.

Comprehensive management of acute necrotizing pancreatitis and pancreatic abscess. Achieving reduced mortality rates in patients with necrotizing pancreatitis and pancreatic abscess is possible by employing a comprehensive management plan. Components of the plan include (1) rapid evaluation and assessment of the degree of physiologic and anatomic derangement, the latter by the prompt use of vascular enhanced computed tomographic scan; (2) adequate fluid resuscitation determined by early institution of advanced hemodynamic monitoring; (3) attempts to identify and document septic foci via computed tomography-guided percutaneous aspiration; and (4) aggressive surgical debridement. Close adherence to these policies allowed us to keep mortality in this seriously ill group of patients to 14%. Most deaths occurred in patients who were referred to this service late in the course of their disease. The Acute Physiology and Chronic Health Enquiry (APACHE) II severity of illness index applied at the time of admission proved an accurate predictor of mortality. A score of 25 or greater was highly predictive of death, and a lesser score, of survival.

Mechanism of early ischemic contractile failure. Inexcitability, metabolite accumulation, or vascular collapse? The basis of early ischemic contractile failure was investigated in perfused ferret hearts at 27 degrees C. Isovolumic left ventricular developed pressure fell by more than 50% within 30 seconds of the onset of total global ischemia and reached zero by 5 minutes. Monophasic action potential recordings revealed no decrease in excitability during this period. Phosphorus nuclear magnetic resonance spectra obtained at 30-second resolution showed no significant changes in inorganic phosphate or phosphocreatine during the first 30 seconds of ischemia. Intracellular pH (pHi) and ATP changed even more slowly; therefore, none of these metabolites could account for the rapid fall in force. To gauge the contribution of intravascular pressure, we compared ordinary aortic flow occlusion with tissue-level ischemia induced by massive coronary microembolization at the level of the precapillary arterioles. Functional depression developed significantly more slowly in the microembolized hearts, despite accumulation of inorganic phosphate and protons comparable with that in ordinary ischemia. After microembolization, the time course of functional depression reflected much more closely the concomitant inorganic phosphate and pHi changes. Thus, our results provide novel evidence supporting the importance of vascular collapse in the mechanism of early ischemic contractile failure.

Effects of hypothyroidism on bronchial reactivity in non-asthmatic subjects. The effect of hypothyroidism on non-specific bronchial reactivity was studied in 11 patients without pulmonary disease (mean age 40 (SD 13) years) who had had a total thyroidectomy and radioiodine treatment for thyroid cancer 41 (36) months before the study. All patients when mildly hyperthyroid while having long term thyroxine replacement treatment and once when hypothyroid two weeks after stopping triiodothyronine for the purpose of screening for metastases. Bronchial reactivity was assessed by measuring specific airways conductance (sGaw) after increasing doses of inhaled carbachol (45-1260 micrograms). The dose producing a 35% decrease in sGaw (PD35) was determined from the cumulative log dose-response curve by linear regression analysis. Mean baseline sGaw values were similar when the patients were hypothyroid and when they were hyperthyroid (1.35 (0.36) and 1.41 (0.56) s-1 kPa-1). The interstudy coefficients of variation of baseline sGaw were higher in the thyroid patients than in a euthyroid control group (14% versus 8%). Geometric mean PD35 was lower when the patients were hypothyroid (97 micrograms) than when they were mildly hyperthyroid (192 micrograms). It is concluded that acute hypothyroidism increases non-specific bronchial reactivity in nonasthmatic subjects.

Marker profile of different phases in the transition of normal human ovarian epithelium to ovarian carcinomas. To investigate whether early changes in the transformation of normal ovarian epithelial cells into tumor cells can be detected with monoclonal antibodies, a comparative immunohistochemical study was performed on normal human ovarian mesothelial cells, cystomas, cystadenomas, ovarian carcinomas, as well as granulosa cell tumor. Using monoclonal antibodies against different keratin subtypes, it was shown that mesothelial cells, ovarian cysts, cystadenomas, and carcinomas all reacted positively with broad-spectrum anti-keratin monoclonal antibodies (MAbs), as well as with MAbs to keratins 7, 8, 18, and 19. Keratins 4 and 13 were not found in mesothelial cells, but positive groups of cells were identified in several cystomas, adenomas, and carcinomas. While mesothelial cells did not react with the pan-epithelial marker BW495/36, invaginating metaplastic mesothelial cells, inclusion cysts, cystomas, adenomas, and carcinomas showed an increasing reactivity with BW495/36, with an increasing degree of malignancy. The reactivity of MAbs against ovarian carcinoma-associated antigens (OV-TL 3, OC 125, MOv 18, and OV-TL 10) was limited to weak staining reaction in some mesothelial cells but were found to be positive on more than 50% of the ovarian cystadenomas and more than 90% of the ovarian carcinomas. Thecal and granulosa cells of primordial, primary, and secondary follicles all reacted positively with antibodies to the broad-spectrum keratins OV-TL 12/5 and RCK 102, and to keratins 8 and 18, but not with keratins 4, 7, 13, and 19. These keratins decreased or disappeared in granulosa cells of mature follicles (Graafian follicles), whereas granulosa cell tumors did not react with anti-keratin antibodies. The reactivity of BW 495/36 was negative or limited to traces in some granulosa cells. Ovarian carcinoma-associated antigens were not expressed in granulosa cells or granulosa cell tumors. The data indicate that mesothelial cells undergoing metaplastic changes finally resulting in ovarian cystadenomas (and carcinomas) initiate the synthesis of a 200-kd glycoprotein recognized by MAb (BW 495/36), the production of ovarian carcinoma associated antigens, in addition to focal production of keratin 4 and/or 13, as seen in several samples. The granulosa cell tumors decrease or switch off their keratin production and remain negative for the 200-kd glycoprotein and the ovarian carcinoma-associated antigens.

Serum acute phase proteins after orthotopic liver transplantation. Acute phase proteins were measured in six patients before liver transplantation and for 72 h after orthotopic liver transplantation. The ability of the donor liver to mount an acute phase response was demonstrated, although the response was less than that seen in other groups of patients in whom this has been studied. Because of the reduced response to stress, the value of these measurements as indicators of liver function in this group of patients is limited.

Subarachnoid hemorrhage caused by a fungal aneurysm of the vertebral artery as a complication of intracranial aneurysm clipping. Case report. Intracranial aneurysms are an uncommon manifestation of fungal infection. A case is described in which the formation of an aneurysm followed an intracranial intraoperative Aspergillus infection attributable to a long period of preoperative antibiotic medication and immunosuppressive therapy with steroids.

Evidence of hibernating myocardium by a new transesophageal echocardiographic technique. Reversal of resting wall motion abnormalities after successful coronary angioplasty were documented in a patient with the use of a novel approach to stress testing. Transesophageal stress echocardiography utilizes transesophageal atrial pacing to provoke myocardial ischemia while the left ventricular contractility is being monitored by means of transesophageal echocardiography. The potential use of this technique is illustrated in this report.

Calculated risk of chromosomal abnormalities in twin gestations. Genetic counseling concerning the risks of chromosomal abnormalities in twin gestations can be difficult; the risk of amniocentesis is weighed against that of chromosomal abnormalities in either one or both of the twins. Because most twins are dizygotic (each with a risk a priori of aneuploidy), the chance that one of the fetuses is affected is greater than would be expected for a singleton. Only three possibilities would result in either one or both twin's being affected: 1) dizygotic twins with one fetus affected, 2) dizygotic twins with both fetuses affected, and 3) monozygotic twins with both fetuses affected. Using existing tables of estimated risks of chromosomal abnormalities in singleton gestations and mathematically derived formulas, we created tables defining the age-related risks of chromosomal abnormalities in twin gestations. According to these tables, a patient at 33 years of age with a twin gestation has a risk of Down syndrome in at least one of her twins equivalent to that of a 35-year-old with a singleton. Prenatal genetic testing should be considered for women with twins at a younger age than the traditional 35.

DNA sequence analysis of three inhibitor-positive hemophilia B patients without gross gene deletion: identification of four novel mutations in factor IX gene. Three hemophilia B patients with anti-factor IX antibodies who had no detectable gross deletion of the factor IX gene by Southern blotting analysis were investigated at the molecular level. All eight exons, accompanied by their splicing junction sites and presumptive promoter regions of the factor IX gene in these patients (total 5.5 kb in length) were amplified with the use of the polymerase chain reaction, followed by complete nucleotide sequence analysis. Three different types of novel single base substitutions and a 2 base-pair nucleotide deletion were identified. Patient HB-5 had two point mutations in his factor IX gene. One was located at the promoter region at nucleotide -793 and the other (C-to-T transition) was found in exon VI of the gene changing Gln-191 to a stop codon. Patient HB-6 had a point mutation (G-to-A) in the splice acceptor site, which interrupted the normal splicing of the last intron G. A small two-nucleotide deletion in exon III was detected in patient HB-7 and yielded frameshifted amino acids and terminated by a stop codon. These resuslts suggest that not only the gross gene deletion of factor IX gene but also the point mutations or small nucleotide deletion that may cause the interruption of coding informations for mature protein synthesis is predisposed to development of anti-factor IX inhibitors in patients with hemophilia B.

Internal capsule plaque and tonic spasms in multiple sclerosis. A patient developed hemilateral tonic spasms associated with a relapse of multiple sclerosis. An area of demyelination in the right internal capsule was observed on a magnetic resonance imaging scan. This lesion was not detectable on a second magnetic resonance imaging scan 10 months after the spasms had ceased. Paroxysmal symptoms in multiple sclerosis may represent transient phenomena related to inflammation in acute plaques.

Timing of corticosteroid treatment. Effect of lung lymph dynamics in air injury in awake sheep. In paired experiments, we studied the effects of high-dose methylprednisolone on the acute pulmonary injury caused by 4 h of venous air embolization in 19 chronically instrumented, unanesthetized sheep with lung lymph fistulas. We compared the effect of methylprednisolone (30 mg/kg intravenous bolus) given before embolization, early (1 H) in the course of embolization, late (3 h) in the course of embolization, or after embolization (at the beginning of the recovery period). We measured pulmonary hemodynamics and lymph dynamics. In six sheep we also fixed lung tissue for semiquantitative histology, and in some we measured leukocyte concentrations in blood and in pulmonary lymph. Methylprednisolone did not significantly affect pulmonary hemodynamics but it largely prevented lung injury when it was given before embolization. It also lessened the degree of lung injury when it was given during embolization, although this effect became less marked as treatment was delayed. Methylprednisolone had no effect on lung injury when given after embolization was completed (4 h). We found fewer leukocytes attached to air emboli and fewer endothelial cell gaps in the lungs of sheep given methylprednisolone as prophylaxis. Leukocyte counts were lower in lung lymph and higher in the circulating blood of methylprednisolone-treated sheep. We conclude that methylprednisolone has a preventive effect on air embolism lung injury, such that its effect is greater when given earlier during the development of injury.

Hospitalization and the cognitive deficits of schizophrenia. The influences of age and education. The study investigated the relationship between length of hospitalization and increasing cognitive deficit in schizophrenics. Using Halstead-Reitan Battery data obtained from 245 schizophrenic patients, multiple regression analyses were performed using age, education, and length of hospitalization as independent variables and various summary test indices as dependent variables. These analyses showed that there was not a statistically significant change in percentage of explained variance when length of hospitalization was entered into the multiple regression equations. On the basis of these analyses, it was concluded that the association between increasing deficit and length of hospitalization experienced by schizophrenic patients is no greater than what would be anticipated on the basis of aging.

Prostacyclin but not phentolamine increases oxygen consumption and skin microvascular blood flow in patients with sepsis and respiratory failure. Inadequate tissue oxygenation may occur in critically ill patients with sepsis despite an apparently adequate O2 transport (QO2), and this may contribute to the development of an O2 debt and also to multiple organ failure. It has been shown that increasing QO2 by infusing a vasodilator may reveal this O2 debt in septic patients. To investigate whether the site of action of vasodilators may be of importance in unmasking such an O2 debt, we administered prostacyclin, a prostaglandin with a preferential effect on the microcirculation, and phentolamine, an arteriolar vasodilator, in 11 patients studied during the first 48 hours after the onset of sepsis, and compared their effect on whole body oxygen consumption (VO2) and skin microvascular blood flow. The results demonstrated that increasing QO2 by prostacyclin but not by phentolamine significantly increases VO2 in critically ill patients with sepsis. The site of action of vasodilators may therefore play an important role in their ability to unmask an O2 debt.

Autograft versus allograft for benign lesions in children. Benign bone lesions in children are often so large in size that there is not an adequate amount of bone available for an autograft to fill the resultant cavity after surgical curettage. This study compared autografts and allografts with respect to the time required and the success of graft incorporation. Fifty-four patients with 61 lesions were studied. Lesions were classified as small volume (less than 60 cc) or large volume (more than 60 cc) and were separated into four groups: small-volume autograft, large-volume autograft, small-volume allograft, and large-volume allograft. Allografts appeared comparable to autografts when small-volume lesions were treated. The healing time was slightly longer for allografts with an average period of 21 months versus 27 months for autografts. Autografts were superior to allografts in rate and completeness of healing for solitary large lesions. This increased efficacy presumes a somewhat older child in which an adequate amount of bone is available for an autograft. A young child with multicentric or polyostotic lesions can still achieve successful incorporation with allografts. In this study, 38% healed completely and 29% healed partially. Allografts have a distinct place in the treatment of benign bone lesions in children.

A paradigm for restenosis based on cell biology: clues for the development of new preventive therapies. Angioplasty causes substantial injury to the coronary artery intima and media that is unrecognizable by angiography. On the basis of a substantial body of research in oncology and wound healing, it is hypothesized that restenosis is a manifestation of the general wound healing response expressed specifically in vascular tissue. The temporal response to injury occurs in three characteristic phases: inflammation, granulation and extracellular matrix remodeling. The specific expression of these phases in the coronary artery leads to intimal hyperplasia at 1 to 4 months. The major milestones in the temporal sequence of restenosis are platelet aggregation, inflammatory cell infiltration, release of growth factors, medial smooth muscle cell modulation and proliferation, proteoglycan deposition and extracellular matrix remodeling. Each step has potential inhibitors that could be used for preventive therapy. Resolution of restenosis, however, probably requires both creation of the largest possible residual lumen and substantial inhibition of intimal hyperplasia.

Comparison of ventricular arrhythmia induction with use of an indwelling electrode catheter and a newly inserted catheter. Two methods of serial electrophysiologic testing are in widespread use. Most commonly, the electrode catheter is removed after each study and a new catheter reinserted through the femoral vein for every subsequent test. An alternative method employs an electrode catheter that remains in place during several days of serial testing. Little is known about differences between these two methods with respect to the likelihood of induction of arrhythmia or the frequency of complications. To determine whether inducibility of sustained arrhythmia is altered or if the frequency of complications is unacceptably high with use of an indwelling catheter, a prospective randomized study was conducted in 78 patients. Each patient underwent baseline testing, several days of electropharmacologic testing with an indwelling catheter, a 24 h drug elimination period and placement of a new electrode catheter. Ventricular stimulation studies were then performed in each patient with both the indwelling and new electrode catheters. No differences were found between the indwelling and new catheter tests with respect to induction of arrhythmia, number of extrastimuli required to induce arrhythmia, rate of arrhythmia or requirement for cardioversion. Ventricular pacing thresholds were higher and effective refractory periods were slightly longer when measured with the indwelling catheter. Complications related to the 156 catheter insertions included two that may have been related to the indwelling catheter (one episode of staphylococcal sepsis and one presumed pulmonary embolism) and four that were related to invasive procedures (pneumothorax in all). There were no long-term adverse sequelae of these complications.

Acquired retinal arteriovenous communications in occlusive disease of the carotid artery. Retinal arteriovenous communications proximal to extensive areas of complete vascular closure developed in three patients with occlusive disease of the carotid arteries. In one case, the authors document the development of the arteriovenous communications through successive enlargement of small retinal vessels after progressive signs of retinal ischemia in the form of narrowed retinal arteries, venous dilation and beading, microaneurysms, retinal dot and blot hemorrhages, cotton-wool spots, and capillary nonperfusion. The development of arteriovenous communications in carotid occlusive disease has not been described previously.

Differential light scattering cuvettes for the measurement of thromboemboli in high shear blood flow systems. Newly developed optical scattering cuvettes were constructed as a modification of our existing 1.0 mm and 3.0 mm internal diameter (ID) cuvettes to facilitate the measurement of platelet microemboli ranging from 20 microns to 1,000 microns diameter in whole blood in 0.9 mm ID flows ranging from 250 to 4,000 ml/min. A perturbation solution to the one-speed radiative transport equation was used in the design and calibration of these cuvettes. A series of tests were performed with these cuvettes in an extracorporeal left ventricular assist device bovine model, and in a recirculating closed-loop flow system containing anticoagulated whole baboon blood, to determine to what extent they affect platelet and erythrocyte function ex vivo and in vitro. Serial hemolysis tests, thromboxane radioimmunoassay measurements, platelet counts, and activated partial thromboplastin times were measured. All of these tests with cuvettes in the extracorporeal and in vitro circuits were statistically indistinguishable from baseline measurements, suggesting the usefulness of this system for the measurement of microemboli in blood-contacting materials of extracorporeal circuits and cardiac assist devices.

Results of radiation therapy in carcinoma of the base of the tongue. The Curie Institute experience with about 166 cases. Between 1960 and 1980, 166 patients with squamous cell carcinoma of the base of the tongue were treated with primary irradiation at the Curie Institute (Paris, France). Distribution according to the TNM system 1978 International Union Against Cancer (UICC) was the following: 22 T1 lesions, 47 T2 lesions, 64 T3 lesions, and 33 T4 lesions. Regional nodes were not palpable in 50 cases, 35 had N1 nodes, 12 had N2 nodes, and 69 had N3 nodes. All patients received external beam radiation. The 2-year, 3-year, and 5-year overall survival rates for all patients were, respectively, 45%, 37%, and 27%. Local control was significantly related to the initial status of the primary, to the tumor regression at the end of the radiation therapy, and to the histologic differentiation. The 2-year local control was 96% for T1 lesions, 57% for T2 lesions, 45% for T3 lesions, and 23% for T4 lesions. Local control was 70% if the tumor regression was complete at the end of the treatment and 27% if the tumor regression was partial. No significant differences were found in primary local control with respect to degree of infiltration, age, and dose of radiation therapy over a dose of 60 Gy in 6 weeks. The 3-year regional control was 86% for N0, 78% for N1, and 60% for N2 and N3. Among the tumor characteristics analyzed, the most useful ones for predicting local control and survival were clinical tumor staging parameters and tumor radiation-induced regression. A new therapeutic approach based on the evaluation of the tumor regression at 50/55 Gy is under discussion.

Embolism of cerebral tissue: a cause of coagulopathy and cerebral infarction? Report of a case. We report a case of potentially survivable closed head injury, which was complicated by disseminated intravascular coagulation and bilateral cerebral infarction. Autopsy disclosed pulmonary emboli composed of cerebral tissue. We suggest that the entry of brain tissue into the systemic blood circulation caused severe disseminated intravascular coagulation, with consequent thrombosis of cerebral veins and spreading infarction.

Asymptomatic periapical radiolucent lesion found in an area of previous trauma [published erratum appears in J Am Dent Assoc 1991 Feb;122(2):18] The case of an anterior mandibular radiolucent area, which unexpectedly yielded salivary gland tissue, is described. Salivary gland depressions in the posterior mandible are readily recognized because of their almost pathognomonic radiographic appearance. A salivary gland inclusion in the anterior mandible in the proximity of teeth may create a diagnostic dilemma where superimposed periapical pathosis is present. The clinical importance lies in the recognition and appropriate treatment of the lesion. For the anterior salivary gland inclusion, a biopsy and a microscopic examination provide the most reliable diagnosis.

Sudden death due to right ventricular cardiomyopathy. A 21-year-old man died suddenly at a small party. He had had no clinical signs of cardiac disease except for a slightly abnormal electrocardiogram (occasional premature ventricular contractions) since he was 15 years of age. Autopsy examination revealed cardiomegaly (469 g), with right atrial and ventricular dilatation. The right ventricular myocardium was massively replaced with adipose tissue, and there was one isolated fatty lesion in the right side of the ventricular septum. There were no congenital malformations such as a septal defect or valvular deformity. Histologically, muscular fibers remaining in the right ventricular wall showed neither degenerative nor inflammatory changes. An isolated lesion of the ventricular septum consisted of almost complete replacement of the muscle bundles with adipose tissue. Such a pathologic condition has recently been termed right ventricular cardiomyopathy. Postmortem examination is necessary to make a definite diagnosis of the disease, because in most adult cases of the disease, sudden death occurs before there have been any critical signs.

Omeprazole enhances the efficacy of pancreatin (pancrease) in cystic fibrosis. We studied the effect of the addition of omeprazole (20 mg once a day) to treatment with pancreatin (Pancrease, Cilag, Herentals, Belgium), two or four capsules three times a day, on fecal fat excretion in a double-blind, crossover fashion in nine patients with cystic fibrosis having persistent steatorrhea while taking Pancrease, two capsules three times a day (mean fecal fat excretion, 22.3%; range, 12% to 44%). Neither doubling of the dose of Pancrease nor addition of omeprazole to the lower dose of Pancrease significantly reduced fecal fat excretion (mean, 19.6% [range, 10% to 34%]; mean, 16.4% [range, 6% to 32%], respectively). However, addition of omeprazole to the higher dose of Pancrease (four capsules three times a day) significantly reduced fecal fat excretion when compared with the two doses of Pancrease alone (mean, 10.7%; range, 4% to 25%; P less than 0.01). We conclude that adjunct therapy with omeprazole reduces fecal fat excretion in cystic fibrosis provided that a high dose of Pancrease is supplied.

Is local recurrence of minor importance for metastases in soft tissue sarcoma? The authors analyzed the relationship between treatment, local recurrence, and metastases in a population-based series of 375 patients with soft tissue sarcoma of the extremities and the trunk wall. Treatment was inadequate (marginal excision alone) in 107 patients, local recurrence occurred in 112, and 128 patients developed metastases. Local recurrence was 3.5 times more common after inadequate treatment than after adequate and 2.5 times more common in patients with metastases than in those without. However, metastases were only 1.2 times more common after inadequate treatment than after adequate. Of the 128 patients who developed metastases, 63 had local recurrence and 65 had not. In these two subgroups the timing of metastases and the distribution of clinicopathologic factors--age, sex, tumor size, localization, depth, histotype, and malignancy grade--were similar. These findings indicate that local recurrence is of minor importance for development of metastases in soft tissue sarcoma. The increased local recurrence rate in metastatic tumors may be an expression of the aggressiveness of the primary tumor; highly malignant tumors combine a potential both for local and distant spread.

Control of immediate postoperative pain with topical bupivacaine hydrochloride for laparoscopic Falope ring tubal ligation. Conflicting reports exist in the literature on the effectiveness of topical local anesthetic applied to the serosal surface of the fallopian tubes for the control of immediate postoperative pain after mechanical (band or clip) tubal ligation. Sixty-four patients were studied prospectively during outpatient laparoscopic Falope ring tubal ligation using the modified McGill Present Pain Intensity Scale. Patients randomly assigned to four groups received topical bupivacaine hydrochloride on both fallopian tubes, the right tube only, or the left tube only, or received none (controls). A unique study design was incorporated which allowed the untreated fallopian tube to serve as a within-subject control for each patient receiving unilateral treatment. Statistical analysis confirmed significant benefit when both fallopian tubes were treated as compared with no treatment (P less than .05). There was also consistent evidence of decreased immediate postoperative pain perception on the treated side for patients receiving unilateral treatment. The value of topical bupivacaine was demonstrated by both subjective patient response (McGill Pain Scale) and reduced need for pain medication before outpatient discharge. Our data support the value of topical bupivacaine applied to the serosal surface of the fallopian tubes for the reduction of postoperative pain after outpatient laparoscopic mechanical (band or clip) tubal ligation.

Visceral perception in health and functional dyspepsia. Crossover study of gastric distension with placebo and domperidone. The symptoms of functional dyspepsia are still unexplained. To evaluate the possible role of abnormal visceral perception, we studied the symptomatic responses and the pressure variations during progressive gastric distension in 10 female healthy control subjects (mean age 33.6 years) and in 10 female patients with functional dyspepsia (mean age 35.2 years). A rubber balloon was positioned 4 cm below the lower esophageal sphincter (LES) and inflated with progressively larger volumes of air by steps of 50 ml; pressures at the gastric fundus and at the LES were continuously recorded by perfused manometric catheters. Each subject was studied on two separate occasions after randomized double-blind administration of either placebo or 20 mg of domperidone. Symptomatic responses and the manometric data were analyzed at the time of the initial recognition of distension (bloating step) and at the time of reporting pain or up to a maximum of 700 ml of balloon inflation (pain or 700-ml step). On placebo, the volumes of gastric distension were more than two times lower in patients than in control subjects at the bloating step (185 +/- 32 ml vs 470 +/- 40 ml, P = 0.001) and at the pain or 700-ml step (265 +/- 54 ml vs 600 +/- 34 ml, P less than 0.005), while the pressure gradients (pressure at inflation steps minus baseline pressure before beginning inflation) were not statistically different between the two groups.

Increasing the yield of ventricular tachycardia induction: a prospective, randomized comparative study of the standard ventricular stimulation protocol to a short-to-long protocol and a new two-site protocol. Programmed ventricular stimulation with a standard protocol that used up to three extrastimuli was compared prospectively with a short-to-long protocol and a two-site protocol in 77 consecutive patients undergoing electrophysiologic study in an attempt to increase the yield of ventricular tachycardia (VT) induction. The short-to-long protocol uses a train of eight stimuli at a short cycle length and up to two extrastimuli. The two-site protocol is similar to the standard protocol but delivers the last extrastimulus via a second spatially separated right ventricular catheter. Patients were divided into two groups based on indications for study: group 1 included 45 patients with syncope, nonsustained VT, or both, and group 2 included 32 patients with a history of sustained VT, sudden cardiac death, or both. The yield of VT induction with the short-to-long protocol was less than that with the standard protocol. In none of the patients in group 1 in whom the standard protocol results were negative did the short-to-long protocol produce sustained VT. Only two patients, both in group 2, had sustained arrhythmias induced by the short-to-long protocol when the standard protocol results were negative: one had sustained VT induced and one with long QT syndrome had ventricular fibrillation (VF) induced with the short-to-long protocol. However, the short-to-long protocol failed to induce sustained VT in seven patients in whom the standard protocol produced sustained VT. All seven of these patients required three extrastimuli with the standard protocol for induction of VT.

Predictive value of congenital hypertrophy of the retinal pigment epithelium as a clinical marker for familial adenomatous polyposis. One hundred forty-eight members of 53 kindreds with familial adenomatous polyposis (FAP) were examined for congenital hypertrophy of the retinal pigment epithelium (CHRPE) and extracolonic manifestations (ECM) to assess the value of CHRPE as a predictive marker for FAP. Based on eye examination results, the families were divided into 2 groups. In a first group of 34 families, all 61 members diagnosed as having polyps and 13 of the 33 patients at risk had 4 or more lesions distributed in both eyes. By contrast, in a second group of 18 families, all 32 polyposis patients and all 18 members at risk had less than 4 lesions. Extra-colonic manifestations were present in 26 of 34 families in the first group and in 11 of 18 families in the second group. Data on one family with ambiguous ancestry were reviewed separately. The existence of 4 or more CHRPE lesions distributed in both eyes seems to be a congenital marker for FAP, present in 65.4 percent of families. When present in a family: 1) it is found in all diagnosed patients in that family, 2) can therefore be considered predictive for the development of polyps in other family members who carry the trait, and 3) if confirmed by longer follow-up, may possibly preclude members without the trait from further evaluation and surveillance.

Mitral valve replacement in the first year of life. From 1973 through 1987 25 patients underwent mitral valve replacement in the first year of life for mitral stenosis and mitral regurgitation. The patients with mitral stenosis included two with mitral arcade, two with supravalvular mitral stenosis with hypoplastic mitral valve, and one with parachute mitral valve. Included in the group of patients with mitral regurgitation were 12 with atrioventricular canal defect, six with chordal and leaflet defects, one with Marfan's syndrome, and one with bacterial endocarditis. Prostheses included 12 Bjork-Shiley (17 mm), seven St. Jude Medical (19 mm in four, 21 mm in three), five stent-mounted dura mater valves (12 mm to 16 mm), and one porcine xenograft (19 mm). In four patients the valves were placed in the left atrium in a supraannular location. There were nine operative (atrioventricular canal defect seven, mitral regurgitation two) and five late (atrioventricular canal defect four, mitral stenosis one) deaths, giving actuarial 1- and 5-year survival rates of 52% and 43%, respectively. All 6 patients with tissue valves died; the four with supraannular mitral valve replacement survived. Since 1983 operative mortality has been reduced to 0% (70% confidence limits 0% to 24%). Nine patients required a second mitral valve replacement for prosthetic stenosis 5 to 69 (mean 30) months after the original mitral valve replacement (one operative death). Because of improvements in repair of atrioventricular canal defect in infancy, the need for mitral valve replacement at atrioventricular canal defect repair has decreased. Although valvuloplasty has been advocated for repair of congenital mitral valve disease and is applicable in some infants with mitral regurgitation, mitral valve replacement is frequently unavoidable for congenital mitral disease and can now be accomplished at a low operative risk, even when the prosthesis has to be positioned supraannularly.

Papillary carcinoma of the thyroid with mucoepidermoid features. The significance and differential diagnoses of signet-ring cells found in the fine-needle aspirate of metastatic mucoepidermoid carcinoma from the thyroid are reported and discussed. The primary tumor occurred in a 35-year-old man, who had a history of neck irradiation during his childhood. Despite postoperative treatment with 60 Gy external radiation and 1,200 mCi 131I, the patient has at present--12 years after the initial operation--progressive disease with local recurrence in the neck as well as lung metastases.

Cytomegalovirus colitis in AIDS: presentation in 44 patients and a review of the literature. As part of a double-blind, placebo-controlled study of ganciclovir in cytomegalovirus (CMV) colitis, the clinical characteristics of 44 patients enrolled at one center were analyzed in detail. All were homosexual men who had CMV on colonic biopsy. CMV colitis was the index diagnosis for acquired immune deficiency syndrome (AIDS) in 11 (25%) of the 44 patients. All had diarrhea, but it was intermittent in 13 patients (30%). Bleeding was uncommon, but 35 patients (80%) were febrile (median temperature of 38.9 degrees C). Weight loss was reported by 39 patients (89%), among whom the median loss was 6.8 kg. Endoscopy revealed normal colonic mucosa but CMV on biopsy in 11 patients (25%). Colonoscopic biopsies positive for CMV were found only in the cecum in 7 (39%) of 18 patients. Most patients (54%) had received zidovudine before the diagnosis of CMV colitis. The median time to the development of CMV colitis after the diagnosis of AIDS was 16 months in those patients who had received zidovudine and 3 months in those who had not (p less than 0.02). We conclude that CMV colitis can present early in AIDS and often with such nonspecific signs as fever, intermittent diarrhea, weight loss, and hematochezia. Importantly, it can appear normal on colonoscopy and occurs frequently only in the right colon, necessitating full colonoscopy and multiple biopsies for accurate diagnosis.

Ki-B5: a monoclonal antibody unrelated to CD45 recognizes normal and neoplastic human B cells in routine paraffin sections. In the search for immunoreagents appropriate for the histopathologic diagnosis of malignant B-cell lymphomas in routinely processed paraffin sections, a new monoclonal antibody, Ki-B5, was generated using a high-grade B-cell lymphoma as the immunogene. Ki-B5 is a mouse IgG1/kappa that recognizes five protein fractions of about 84, 82, 55, 48, and 27 Kd after biosynthetic radiolabeling and immunoprecipitation. Protein fractions with the molecular weights of approximately 84 and 82 Kd were expressed on the cell surface and show that Ki-B5 is probably unrelated to CD45. It was possible through electron microscopy to visualize the membrane-bound portion of Ki-B5. Extensive immunohistologic studies on normal human tissue and various neoplasias demonstrated the high specificity of Ki-B5 to normal human B cells and a minor subgroup of plasma cells. Except for ML-2, which is a myelomonocytic human cell line, Ki-B5 exclusively recognized the B-cell lineage, including EB-3, BALL-1, and NALM-1. All carcinomas, sarcomas, and malignant melanomas tested with Ki-B5 were negative. Although normal granulocytes and monocytes were constantly negative, three of eight myelomonocytic leukemias coreacted with this antibody. Eight of the 57 T-cell lymphomas studied were positive to Ki-B5. Five were classified as lymphoblastic, two represented T8-CLL, and one was classified as immunoblastic T-cell lymphoma. Only 3 of 126 cases of B-cell lymphoma, including rare types not considered in the current classifications, were negative to Ki-B5. Plasmacytomas were also negative, except for one case. Irrespective of the cases of lymphoblastic lymphoma and plasmacytoma, Ki-B5 represents a new monoclonal antibody appropriate for the diagnosis and immunophenotyping of malignant lymphomas in routinely processed paraffin sections.

Hepatocellular carcinoma within siderotic regenerative nodules: appearance as a nodule within a nodule on MR images. Large regenerative nodules in cirrhotic livers may accumulate iron and develop internal iron-poor foci of hyperplasia or malignancy. Magnetic resonance examinations were performed on 23 patients with biopsy-proved cirrhosis. A "nodule-within-nodule" appearance was noted in two patients. This appearance consisted of markedly low intensity of a large nodule on gradient-echo images, with one or two internal foci that were isointense to the liver. Each of the large nodules was 2 cm in diameter, and each of the internal foci was less than 1 cm. Serum alpha-fetoprotein levels were normal in both patients. Aspiration biopsy performed in one patient failed to show malignancy, but histologic confirmation of hepatocellular carcinoma was obtained eventually in both cases. The nodule-within-nodule sign, which reflects the unique histopathology of hepatocellular carcinoma in large siderotic regenerative nodules, is strongly suggestive of early hepatocellular carcinoma, even if serologic markers and biopsy results do not support this diagnosis.

Work and power in gait of stroke patients. Biomechanical analysis of the work and power patterns involved in gait provides insight into the nature of gait deficits and suggests methods for improvement. The purpose of this study was to describe the work and power characteristics during gait for both limbs of hemiplegic patients, and to determine the work and power variables related to self-selected speeds of walking. The gait of 30 ambulatory adults between the ages of 47 and 79 years was studied using two-dimensional cinematography and force-plate data in a link-segment model. About 40% of the positive work required for walking was performed by the muscles of the affected side. Major contributors were the ankle plantar flexors, hip flexors, and hip extensors. The results suggest interdependence between the limbs and between muscle groups of the same limb; a need for further research is indicated.

Transbronchial biopsies in children after heart-lung transplantation. Sixty transbronchial biopsies have been performed in eight children after heart-lung transplantation. The selection of fiber-optic bronchoscope or a small (4 mm; 30 cm) rigid bronchoscope was made according to the size of endotracheal tube required at surgery. If the endotracheal tube was size 7.5 or greater, a fiber-optic bronchoscope was used, whereas if the endotracheal tube size was below 7, a rigid bronchoscope was used. For the diagnosis of lung rejection, the histology of biopsies revealed a sensitivity of 91% and specificity of 69% (similar to the result in adults). The histology also distinguished lung infection from rejection. Complications included three pneumothoraces and two clinically significant episodes of hemorrhage, one of which led to a cardiorespiratory arrest, which may have been caused by hypoxia. As a result, arterial oxygen saturation is now monitored during the procedure using a pulse oximeter.

The effects of tumor necrosis factor on intestinal structure and metabolism. Tumor necrosis factor (TNF), a polypeptide produced predominantly by activated macrophages, is an important mediator of sepsis. We analyzed the specific metabolic changes that occur in the gut following TNF administration. Following general anesthesia, hemodynamic and metabolic indices were measured serially in control dogs (n = 7) and animals receiving a continuous sublethal intravenous infusion of TNF (0.57.10(5) IU/kg/6 hours, n = 7). During TNF infusion mean arterial pressure gradually decreased despite fluid administration, which maintained wedge pressure and cardiac index, which were similar to control animals. While TNF significantly reduced intestinal blood flow to 12 +/- 3 mL/min/kg compared to 28 +/- 3 mL/min/kg (p less than 0.01) in controls, intestinal oxygen consumption was maintained due to an increased extraction rate. Despite hypoperfusion the intestinal exchange of metabolic substrate (glucose, lactate, pyruvate, alanine, glutamine, glutamate, and ammonia) was comparable between the control and TNF-infused animals. However, when substrate carbon balance across the intestinal tract was calculated, it appeared that there was a limitation in fuel availability in the TNF animals. This may be due to competition for fuel between the gut and other major organs. Fuel limitation may jeopardize rapid cell proliferation and mucosal repair and with regional hypoperfusion these processes may account for the mucosal ulcerations observed at the termination of the study.

Spontaneous pneumothorax: marker gas technique for predicting outcome of manual aspiration [published erratum appears in BMJ 1991 Mar 23;302(6778):697] OBJECTIVE--To determine whether in a patient with spontaneous pneumothorax the presence or absence of a pleural leak can be shown at the time of manual aspiration by use of a marker gas. Also, to find out if the technique can predict whether manual aspiration will be successful, hence avoiding the need for intercostal tube drainage. DESIGN--Prospective study of 25 episodes of pneumothorax during which patients breathed air from a Douglas bag that contained chlorofluorocarbon gases from a metered dose inhaler while the pneumothorax was aspirated. SETTING--Medical unit of a district general hospital. PATIENTS--22 patients who presented over nine months with acute pneumothorax. MAIN OUTCOME MEASURES--Presence or absence of chlorofluorocarbon marker gases in the aspirate. Presence or absence of sustained re-expansion of the affected lung in the chest radiograph. RESULTS--Marker gas was detected in the aspirate from 16 out of 25 pneumothoraces. Of these, 13 required intercostal tube drainage because of failure of the lung to re-expand. Marker gas was not detected in nine cases, and in all of these cases manual aspiration resulted in sustained re-expansion of the lung. CONCLUSIONS--The presence or absence of a pleural leak during manual aspiration of spontaneous pneumothorax can be shown by using this technique. The absence of marker gas in the aspirate implies that manual aspiration will be successful, whereas its presence predicts, in most cases, either failure of manual aspiration to expand the lung or early re-collapse of the lung.

Characterization of descending inhibition and facilitation from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. Descending influences on the spinal nociceptive tail-flick (TF) reflex produced by focal electrical stimulation and glutamate microinjection in the nuclei reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha) were examined and characterized in rats lightly anesthetized with pentobarbital. Both inhibition and facilitation of the TF reflex were produced by electrical stimulation at identical sites in the NGC/NGC alpha; glutamate microinjection only inhibited the TF reflex. The chronaxie of stimulation for inhibition of the TF reflex was 169 +/- 28 microseconds. Inhibition of the TF reflex by stimulation was produced throughout the NGC and NGC alpha; intensities of stimulation for inhibition were least in the ventral NGC and in the NGC alpha. At threshold intensities of stimulation, inhibition of the TF reflex did not outlast the period of stimulation. Facilitation of the TF reflex was produced at many of the same sites at which stimulation inhibited the TF reflex, but always at lesser intensities of stimulation (mean, 10 microA vs. 43 microA for inhibition, n = 25). Stimulation in the NGC/NGC alpha at threshold intensities for facilitation or inhibition of the TF reflex did not significantly affect blood pressure. Strength-duration characterization of electrical stimulation and microinjection of glutamate into identical sites in the NGC and NGC alpha suggest that descending inhibition of the TF reflex results from activation of cell bodies in the NGC and NGC alpha.

In vitro model of intestinal crypt abscess. A novel neutrophil-derived secretagogue activity. In order to model crypt abscesses, a histological finding which correlates with disease activity in intestinal inflammation, human polymorphonuclear leukocytes (PMN) were layered onto monolayers of the human intestinal epithelial cell line T84, a crypt-like epithelium which is capable of Cl- secretion. Such PMN-epithelial interaction had no substantial effect on monolayer integrity or function. However, when PMN were stimulated by conditions including those present naturally in the human colonic lumen, monolayers responded with a bumetanide-sensitive short circuit current (Isc) indicative of Cl- secretion, the basis of secretory diarrhea. This Isc response was induced by a neutrophil-derived secretagogue (NDS), which was only active when applied to the luminal surface of monolayers and did not require PMN-epithelial contact. NDS activity is resistant to boiling, acid, and trypsin and passes a 500 nominal mol wt cutoff filter. NDS activity is not secondary to the respiratory burst products O2- or H2O2 and does not appear to be a myeloperoxidase product. We speculate NDS elicited Cl- secretion may contribute to the secretory diarrhea seen in patients with intestinal inflammation and crypt abscesses.

The management of retinal detachments associated with choroidal colobomas by vitreous surgery. We used vitreous surgery to treat seven patients (eight eyes) with complicated retinal detachments associated with choroidal colobomas. All eyes had large choroidal colobomas and no evidence of peripheral retinal breaks. Small, atrophic breaks were detected in five of the eyes and were located in the base of the coloboma in four of the five eyes. Adjunctive surgical techniques were necessary and included cyanoacrylate retinopexy in four eyes, silicone oil tamponade in five eyes, and retinectomy in two eyes. Retinal reattachment was ultimately attained in seven of the eight eyes. The number of surgical procedures ranged from one to five, with an average of three. Postoperative visual acuity of the eyes that underwent anatomically successful procedures ranged from 20/100 to light perception. Proliferative vitreoretinopathy was the most frequent cause of redetachment, occurring in six of the eight eyes.

Swimmer's migraine. Three cases of sudden, severe headache occurring during swimming are described. A 51-year-old female had been engaging in a swimming exercise for about 20 minutes when she suddenly experienced a pulsating headache in the parietotemporal region, accompanied by nausea. A few days later, she experienced a similar episode, again during swimming practice. A 45-year-old male developed a pulsating headache with nausea immediately after diving into a swimming pool, and had a similar attack during diving practice 1 week later. A 32-year-old male developed a pulsating headache accompanied by nausea while swimming in the sea. In all three cases, blood pressure, pulse rate, neurological findings, cervical spinal x-rays, brain CT scans, and hematological findings were normal and the outcome was good. Although these patients' headaches were diagnosed as benign exertional headache, pathophysiologically they appeared to resemble the headache associated with sexual activity.

Renal secretion and hepatic clearance of human multiple renin forms. Human active renin can be separated into at least five forms by isoelectric focusing. The present study assessed the preferential renal secretion and hepatic degradation of renin forms in humans. The renin form profile of secreted renal renin was determined before transplant in an ex vivo kidney donor perfusion system and compared with the peripheral plasma multiple renin form profile of normal subjects. The effect of hepatic degradation on renin forms was assessed in hepatic vein plasma in comparison with infrarenal vena cava plasma in hypertensive patients during renal vein renin studies. The results revealed a significantly greater proportion of the more basic forms in the perfusate of donor kidneys compared with normal plasma. In hypertensive patients the proportion of the more basic renin forms in the hepatic vein was significantly decreased in comparison with the infrarenal vena cava. Thus, the human kidney may preferentially secrete the more basic renin forms. In contrast, the liver preferentially degrades the more basic forms, giving these forms a shorter plasma half-life. The preferential secretion and clearance of the more basic forms of renin may contribute to short-term control of human renin-angiotensin system activity.

Risk factors for white matter changes detected by magnetic resonance imaging in the elderly. We found increased age (p = 0.001) and history or evidence of stroke (p = 0.016) to be significant independent multivariate predictors of the presence and severity of leukoencephalopathy on magnetic resonance imaging brain scans in a mixed population of 35 elderly psychiatric patients and 25 neurologically healthy elderly volunteers. These results suggest that subcortical ischemia, as well as age-related changes that may not be vascular in origin, contribute to the emergence of periventricular and other deep white matter hyperintensities that are commonly seen on the magnetic resonance imaging brain scans of older adults.

Two-way factorial study of alcohol and salt restriction in treated hypertensive men. The aim of this study was to determine whether moderate restriction of dietary salt intake leads to an additional fall in blood pressure in treated hypertensive men who are asked to simultaneously reduce their usual alcohol intake. Sixty-three subjects entered an initial 2-week familiarization period during which they continued their usual alcohol intake and commenced a "low sodium" diet (less than 60 mmol/day) supplemented with 100 mmol sodium chloride per day as enteric-coated tablets. Subjects were then randomly assigned to either drink a low alcohol beer alone for a 4-week period (reducing their self-reported alcohol consumption from 537 to 57 ml/week) or to continue their usual alcohol intake (543 versus 557 ml/week). Within the low and normal alcohol intake groups, subjects were assigned to either a low or normal sodium intake. The low sodium groups continued the sodium-restricted diet but were switched to placebo sodium chloride tablets for the 4 weeks. This resulted in a fall in the 24-hour urinary sodium excretion from 144 to 69 mmol/day. The normal sodium groups continued the low sodium diet but kept taking 100 mmol/day of the sodium chloride tablets, and their urinary sodium excretion remained unchanged (125 versus 142 mmol/day). Regular antihypertensive therapy was continued throughout. Fifty-nine subjects completed the trial. In those who reduced their alcohol intake there was a fall in both systolic blood pressure (-5.4 mm Hg supine, p less than 0.01) and diastolic blood pressure (-3.2 mm Hg supine, p less than 0.01).

Segmental wall motion abnormalities in the absence of clinically documented myocardial infarction: clinical significance and evidence of hibernating myocardium. To determine the frequency and significance of left ventricular wall motion abnormalities in patients without clinical evidence of myocardial infarction, we reviewed the two-dimensional echocardiograms of 252 patients who had no history or electrocardiographic evidence of myocardial infarction and who subsequently underwent coronary angiography. Seventy-seven patients (31%) had one or more segmental wall motion abnormalities. Sixty-six of the 77 patients (86%) had significant coronary artery disease (greater than or equal to 50% luminal diameter stenosis). Seventy-four percent of the patients with coronary artery disease had multivessel disease. The left ventricle was divided into anterior and posterior regions. In the 66 patients, there were 77 separate regions with wall motion abnormalities (49 hypokinesis, 22 akinesis, 6 dyskinesis), including 60 regions (78%) supplied by coronary vessels with greater than or equal to 70% stenosis. Thirty-two patients underwent coronary artery bypass surgery or percutaneous transluminal coronary angioplasty. Follow-up echocardiograms were obtained in 19 patients who had wall motion abnormalities involving 22 regions. Twenty of the 22 regions were revascularized. Wall motion improved in 17 of 20 regions (85%) and returned to normal in 15 regions (75%). We conclude that segmental wall motion abnormalities may be detected by echocardiography in up to one third of patients evaluated for suspected coronary artery disease without documented myocardial infarction. These abnormalities are associated with a high likelihood of multivessel disease as well as with significant narrowing of the artery supplying the region demonstrating abnormal wall motion. Improvement in segmental wall motion abnormalities after revascularization suggests that these areas represent regions of hibernating myocardium.

Acute respiratory tract infections among a birth cohort of children from Cali, Colombia, who were studied through 17 months of age. For this study, 340 children less than 18 months old from a low-income, urban neighborhood in Cali, Colombia, were observed from birth by means of weekly home visits to detect cases of acute respiratory tract infection. All suspected cases were confirmed by trained doctors in a special clinic. Information on symptoms, signs, and potential risk factors was documented prospectively. Etiologic agents were identified in cases of lower respiratory tract infection (LRI). The overall incidence of acute respiratory tract infection was 6.6 cases per child-year at risk. The incidence of upper respiratory tract infection was 4.9 cases per child-year at risk and that of LRI was 1.7 cases per child-year at risk. Crowding in the home was found to be significantly associated with an increased incidence of LRI. Respiratory syncytial virus was the viral agent most frequently isolated from cultures of nasopharyngeal aspirates of children with LRI. Staphylococcus aureus was the bacterial agent most frequently isolated from the blood of patients with LRI.

Acute and chronic bacterial prostatitis: a review of treatment approaches. Some authors describe acute bacterial prostatitis as a self-limiting disease, and as with any other acute septic condition, parenteral broad-spectrum antibiotic therapy is indicated. Chronic bacterial prostatitis, however, is associated with a causative organism persisting unaltered in prostatic fluid and leading to relapsing urinary tract infections. In the 1970s, several workers produced a classification system and bacteriologic localization cultures for establishing the diagnosis of prostatitis. Krieger and Crawford point to an important factor that is omitted in many clinical trials with episodes of chronic bacterial prostatitis in men. If localization studies of the prostate infection are attempted in the presence of bacteriuria, the urine must be sterilized with nitrofurantoin or penicillin G. Urine cultures obtained from first-voided urine, bladder urine, and urine voided after prostatic massage should show no growth, and the expressed prostatic secretion can then be examined for evidence of prostatic infection. This procedure reduces the contamination of the expressed prostatic secretion by the organism from the urinary tract infection. This is important, because antibiotic treatment is determined by the sensitivity of the organism isolated from the prostate as well as by the ability of the antibiotics to penetrate the prostate. Meares outlines the pharmacokinetic features needed for drug diffusion into prostatic fluid and provides detailed information on the physical characteristics of the prostate during acute and chronic bacterial prostatitis. Unfortunately, the choice of an ideal drug cannot be extrapolated from this information because pharmacodynamic principles cannot predict clinical efficacy. Some authors find that sulfamethoxazole-trimethoprim has the best cure rate in the treatment of chronic bacterial prostatitis.

Plasma epinephrine levels in resuscitation with cardiopulmonary bypass. Since the highest plasma epinephrine levels have been recorded during resuscitation, we evaluated the isolated effect of cardiac arrest upon adrenomedullary secretion. We determined plasma epinephrine in dogs resuscitated with cardiopulmonary bypass (CPB) after cardiac arrest periods of 12 (CPB-12; n = 4) or 16 min (CPB-16; n = 5). Through 2 h of CPB and the following 6 h of critical care, there was no difference between CPB-12 and CPB-16 regarding most cardiopulmonary functional variables. Plasma epinephrine was markedly elevated immediately after initiation of CPB (p less than .01 at 1 min CPB vs. basal) and returned rapidly to basal concentrations. Comparison of plasma epinephrine levels between CPB and standard CPR groups showed that responses to cardiac arrest were similar (p greater than .05 at 1 min CPB vs. 11.5 min CPR). We conclude that cardiac arrest is the main or sole determinant of the plasma epinephrine elevation of resuscitation.

Epithelial abnormalities in intestine and kidney of the spontaneously hypertensive rat. A variety of perturbations of calcium metabolism are reported to occur in the spontaneously hypertensive rat (SHR) compared to its genetic control the Wistar-Kyoto rat (WKY), including significant dysfunction of calcium handling by the proximal renal tubule of the SHR, resulting in impaired active calcium transport in the gut and an apparent renal calcium leak. We explored the intestinal and renal epithelia of 12- to 14-week-old SHR and WKY using electron microscopy. Biochemical comparisons of these transport epithelia included measurements of three vitamin D dependent cellular proteins and one structural protein: alkaline phosphatase, intestinal CaBP9K, renal CaBP28K, and villin expression. Electron microscopy demonstrated a patchy loss in microvilli in the SHR, accounting for approximately 10 to 15% of the total microvillar surface. In the kidney, morphological abnormalities were observed only in the proximal renal tubule. Again, there was patchy loss of microvilli from the brush border membrane. In SHR duodenal alkaline phosphatase activity was significantly reduced compared to the WKY (0.145 +/- 0.002 v 0.186 +/- 0.002 integrated extinction/min/micron 3 X 10(3) brush border (P less than .001). Duodenal CaBP9K and renal CaBP28K were significantly reduced in SHR compared to WKY. There were no differences in villin expression. These data are consistent with the previously characterized disturbances of active calcium transport in the intestine and inappropriate renal calcium leak in the SHR. While a possible link between these disturbances and hypertension remains to be determined, this study provides supportive evidence for a primary disturbance in cell calcium handling and transporting epithelia in this form of genetic hypertension.

Cancer mortality in a higher-income black population in New York State. Comparison with rates in the United States as a whole. In the 1980 Census the median family income among blacks in Suffolk County, New York (i.e., $19,604) was much higher than that for American blacks as a whole (i.e., $12,618) and 94.1% of that for American whites (i.e., $20,840), but the proportion below the poverty level was still higher for Suffolk County blacks than for American whites. Observed numbers of deaths from 1979 to 1985 for total cancers and most cancer sites in Suffolk County black men and women were not lower than expected on the basis of age-specific and gender-specific death rates for blacks in the US. Although numbers of deaths from cervical cancer and prostate cancer were slightly lower than expected in Suffolk County blacks versus American blacks, these numbers were still significantly greater than expected on the basis of death rates among American whites. Age-specific death rates for age groups 25 to 44 years to 55 to 64 years tended to be lower in Suffolk County for lung cancers in black men but not for breast cancer in black women. Specific cancer sites, which differ in the direction of the association between incidence and socioeconomic status, age, and gender must be considered in comparisons of cancer mortality by race and socioeconomic level. Implications of the comparisons were discussed with regard to the goal of reducing racial differences in cancer death rates.

Anchorage-independent growth and the expression of cellular proto-oncogenes in normal human epidermal keratinocytes and in human squamous cell carcinoma cell lines. The expression of multiple cellular proto-oncogenes and the in vitro anchorage-independent growth of normal human epidermal keratinocytes and several human squamous cell carcinoma cell lines were studied and correlated. Squamous cell carcinoma cell lines KB, Si Ha, HEp-2, and Fa Du showed high anchorage independency, and MS 751 and A-253 cell lines had minimum independency. However, the normal keratinocytes and the A-431 cell line did not show anchorage-independent growth. Both the normal human epidermal keratinocytes and cancer cell lines expressed multiple proto-oncogenes such as src, erb B-1, abl, fos, raf, H-ras, and myc, and the amount of expression of these oncogenes was notably higher in the cancer cell lines than in the normal keratinocytes. The expression of proto-oncogenes from the monolayer cultures of the cancer cell lines is poorly correlated with the anchorage independency of the cells. These data indicate that the anchorage independency is not directly linked to the expression of specific cellular proto-oncogene(s) of the monolayer cancer cell cultures.

A 27-year experience with splenectomy for Gaucher's disease. Gaucher's disease is an inherited metabolic disorder caused by the defective activity of acid beta-glucosidase and the resultant accumulation of glucosyl ceramide-laden macrophages in the liver, bone, and spleen. Splenectomy is the preferred treatment for patients with Gaucher's disease who develop massive splenomegaly with accompanying hypersplenism and/or mechanical pressure symptoms. The charts of 48 patients with Gaucher's disease undergoing splenectomy at our institution between January 1963 and December 1989 were analyzed to determine the short- and long-term results of this procedure. Thirty-five (73%) patients had total splenectomy, whereas 13 (27%) patients had partial splenectomy. There was one postoperative death (after total splenectomy), and 13 patients (27%) had postoperative complications. Eleven patients (23%) presented with accelerated bone disease after total splenectomy (mean follow-up: 96 months). No patients having partial splenectomy (mean follow-up: 25 months) developed progressive bone disease. Eight patients have died since surgery. All four deaths due to malignant disease occurred in patients after total splenectomy. The results of this largest-ever reported series of splenectomy for Gaucher's disease confirm that while either total or partial splenectomy can be performed with minimal morbidity and mortality, total splenectomy is accompanied by more aggressive bone disease and a predisposition to malignancy. Prospective, randomized trials are needed to substantiate whether partial splenectomy is indeed the treatment of choice for splenomegaly associated with Gaucher's disease.

High mortality among patients with the leukemoid reaction and alcoholic hepatitis. We describe a patient with severe alcoholic hepatitis, markedly elevated white blood cell count, and high fever. After review of the English literature, we discovered reports of other cases similar to our case. The striking feature in all of these cases was a high short-term mortality rate, despite predictions of a favorable outcome. We therefore believe these patients represent a subgroup of patients with alcoholic hepatitis and that the leukemoid reaction is a poor prognostic sign in this disease.

Cervical rotation flaps for midface resurfacing. The midface has long served as a focus for creativity in surgical reconstruction. Full-thickness skin grafts, split-thickness grafts, and distal flaps have long been used to attempt to reduplicate existing anatomy in this area. Recent reconstruction efforts have focused on the creative use of microvascular free flaps for this purpose. This article reports on the use of extensively developed regional rotation flaps as an excellent reconstructive modality for use in this area of the face. The details of surgical incisional planning are given. The nuances of surgical creation of these flaps and their rotation and suspension into place are given. The cases we have done using this technique for the past 3 years are reviewed. Our present indications for use of these flaps and their limitations are given.

Preanaesthetic medication with clonidine. The purpose of this study was to evaluate oral clonidine in a dose of 0.3 mg as a routine premedicant. Sixty-nine normotensive female patients were studied in a randomized double-blind investigation in which clonidine was compared with an inert treatment. Clonidine produced a significant reduction in anxiety (P less than 0.05) and sedation and a reduction in the sleep dose of methohexitone (P less than 0.05). Tachycardia in response to intubation was attenuated by clonidine (P less than 0.05). However, the magnitude of the increase in arterial pressure after intubation was not affected. Intraoperative and postoperative hypotension were common after premedication with clonidine 0.3 mg and caution is urged in its use as a premedicant.

The accuracy of CT scanning in the diagnosis of abdominal and thoracoabdominal aortic aneurysms. As CT scanning has evolved as a reliable clinical tool, the use of angiography in the diagnosis of aortic aneurysmal disease has diminished. Fewer than 25% of patients with aortic aneurysmal disease undergo aortic angiographic evaluation at our institution. A prospective clinical study was undertaken to assess the validity of this policy. One hundred patients with clinical or ultrasonographic evidence of aortic aneurysms were evaluated prospectively during the period July 1987 to December 1989. All patients underwent CT scanning as an initial evaluation. Patients were selected for angiography if they fulfilled any of the following criteria: radiographic evidence of thoracoabdominal or juxtarenal aneurysms, or horseshoe kidney; or clinical suggestion of renal artery stenosis, mesenteric arterial insufficiency, aortoiliac occlusive disease, or lower extremity aneurysmal disease. During this period 19 patients (19%) underwent both CT scanning and angiography. The indications for angiography were thoracoabdominal aneurysms (7), juxtarenal aneurysms (2), clinical evidence of mesenteric insufficiency (1) or renal insufficiency (2), evidence of lower extremity aneurysmal disease (3), or severe aortoiliac occlusive disease (4). Eighty-one patients (81%) underwent CT scanning as the only radiographic evaluation. No patient was adversely affected by elimination of angiographic evaluation. CT scanning revealed inflammatory aneurysms (4), retroaortic renal veins (2), and horseshoe kidney (1). This study suggests that most (81%) patients with aortic aneurysmal disease can be adequately evaluated by CT scanning, and that a very selective policy of angiographic evaluation is indicated.

Abnormal growth patterns and adult short stature in 115 long-term survivors of childhood leukemia. Significant growth retardation was found in 115 survivors of childhood acute lymphoblastic leukemia (ALL) who had completed their growth. These children were diagnosed before 12 years of age and treated on four protocols in a single institution; all received either cranial (n = 78) or craniospinal (n = 37) prophylactic irradiation. Patients' heights at diagnosis were within expected ranges, but final heights were greater than or equal to 1 SD below population means in 74% of cases and greater than or equal to 2 SD in 37%. Effects on growth were more pronounced for children who had received craniospinal irradiation, but decrements were also significant in the cranial irradiation group, with adult heights greater than or equal to 2 SD below population norms in 32%. Growth retardation was significantly greater (P less than .0001) in children who had earlier disease onset. Growth deceleration occurred not only during chemotherapy but during a later period that followed an interval of improved growth in many cases. Thus, late decrements in growth may be missed in studies that do not follow patients until they have attained final heights. These findings indicate that abnormally short stature among survivors of ALL merits further clinical and research attention.

Effect of epidermal growth factor in combination with sucralfate or omeprazole on the healing of chronic gastric ulcers in the rat. Epidermal growth factor (EGF) has been shown to enhance healing of experimental gastric ulcers when given subcutaneously or orally in the drinking water. This effect of EGF occurs without reducing gastric acid secretion. On the other hand, EGF reportedly is excreted rapidly from gastric lumen when administered by intragastric bolus. This suggests that further stimulation of ulcer healing may be expected if EGF is given with an acid-suppressive agent or with an agent allowing EGF to remain in rat gastric lumen at high concentrations. In the present study, EGF administered by gastric intubation at a dose of 10 micrograms/kg, which is three times smaller than reported in previous studies, was evaluated for its effect on acetic acid-induced rat gastric ulcers in combination with sucralfate or omeprazole. Sucralfate is well known selectively to bind proteins covering the ulcer base, and omeprazole is a potent acid-suppressive agent. Prior to the study of combined EGF and sucralfate, oral sucralfate was confirmed to allow endogenous gastric EGF and mouse EGF given exogenously to remain at high concentrations in gastric contents and tissues. EGF and sucralfate (2 g/kg/day) given alone failed to stimulate ulcer healing in submandibularectomized rats (SMR rat) whose endogenous gastric EGF was depleted. However, the combination of both drugs administered at the same doses significantly accelerated ulcer healing in the SMR rat. Omeprazole (200 mg/kg/day) significantly enhanced ulcer healing regardless of removal of the submandibular glands. The combination of EGF and omeprazole further stimulated ulcer healing in the SMR rat.

Polyarteritis nodosa presenting as a biliary stricture. Polyarteritis nodosa, a disease of the media of small and medium-sized arteries, has protean manifestations and many presenting signs and symptoms. Gastrointestinal involvement is common but involvement of the biliary tree is rare. We report a unique case of polyarteritis presenting as a biliary stricture.

Renovascular disease and renal complications of angiotensin-converting enzyme inhibitor therapy Renal complications of angiotensin-converting enzyme (ACE) inhibitor therapy are widely recognized, but few authors have documented the incidence or spectrum of these conditions. In a retrospective study of 530 consecutive patients presenting to our unit as acute uraemic emergencies over a six-year period, 85 (16 per cent) had renovascular disease that was considered to be responsible for their loss of renal function. Twenty-one (4 per cent) patients had uraemia which could be clearly attributable to ACE inhibitor treatment; 18 of these cases were shown to have significant renovascular pathology. Following withdrawal of the ACE inhibitor the renal failure reversed in the majority of patients. We also examined 400 consecutive hypertensive patients referred over a similar period and, although vascular imaging was performed only when it was considered to be clinically indicated, 58 (14.5 per cent) of these patients were shown to have renovascular pathology. A further five patients with stable chronic renal disease were seen to have a deterioration in their glomerular filtration rate coincident with commencement of ACE inhibitor therapy; this reversed when the agents were withdrawn. These observations indicate that significant renovascular disease may be more common than has been hitherto recognized and that injudicious use of ACE inhibitors may result in serious complications. Methods which may minimize such iatrogenic disease are suggested.

Randomized trials in the study of antihypertensive drugs. Heterogeneity in response to antihypertensive drugs can be addressed by randomized trials in individual subjects. In such a trial a patient receives pairs of treatment periods (one period of each pair active drug, one matched placebo, in random order); patient and clinician are blinded to allocation, and treatment targets are monitored. These trials can optimize antihypertensive therapy in clinical practice and facilitate the investigation of new drugs and the study of pathophysiology. Such trials also have potential in helping decide whether common, nonspecific symptoms reported by patients are really drug related.

Synergistic effects of nerve growth factor and granulocyte-macrophage colony-stimulating factor on human basophilic cell differentiation. We have recently shown that nerve growth factor (NGF) promotes human granulopoiesis, specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood. Because the NGF effect was seen in the presence of conditioned medium derived from a human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating factor (GM-CSF), we examined interactions of purified NGF and recombinant human GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated a dose-dependent increase in methylcellulose colony growth at concentrations between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and histamine-positive colonies increased synergistically when NGF was added to rhGM-CSF. Furthermore, because Mo-CM acts with sodium butyrate to promote basophilic differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine production by butyrate-induced, alkaline-passaged HL-60 cells; this was associated with the appearance of metachromatic, tryptase-negative, IgE receptor-positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that differentiation in the basophilic lineage may be enhanced by NGF acting to increase the number of GM-CSF-responsive basophilic cell progenitors.

Studies of myocardial protection in the immature heart. III. Models of ischemic and hypoxic/ischemic injury in the immature puppy heart. This study compares the metabolic and functional effects of three different models of ischemia in the immature heart. The intent was (1) to develop a model of energy-depleted and functionally depressed heart to be used in subsequent studies of myocardial protection and (2) to characterize the biochemical changes following different interventions. Forty-five minutes of normothermic global ischemia produced severe depletion of adenosine triphosphate and creatine phosphate (greater than 70%) but was associated with 85% +/- 10% recovery of left ventricular function. Postischemic functional depression (less than 30% recovery) could be produced by either (1) extending the ischemic duration to 60 minutes or (2) preceding 45 minutes of ischemia by 60 minutes of hypoxic stress (oxygen tension 25 to 30 mm Hg). Neither of these more severe interventions caused more profound depletion of adenosine triphosphate or creatine phosphate, but hypoxic stress produced marked tissue depletion of glutamate (52%) and aspartate (48%) before aortic clamping. Longer ischemia or preceding hypoxia led to greater myocardial accumulation of lactate (greater than 250 versus 104 mumol/gm dry weight) and succinate (18 versus 11 mumol/gm dry weight) during aortic clamping, p less than 0.05 versus 45 minutes of ischemia) and greater postischemic depression and amino acid (greater than 65% aspartate depletion) and carbohydrate (greater than 50% glycogen depletion) metabolism, p less than 0.05 versus simple ischemia. These findings suggest that more severe ischemic/hypoxic models are needed in immature hearts to produce functional depression, and the biochemical analyses suggest the characteristics of metabolic defects that must be corrected to resuscitate these hearts during surgical correction of congenital defects.

Acute urinary retention secondary to Herpes simplex meningitis. We report a case of acute urinary retention in a 24-year-old man with Herpes simplex meningitis without genital lesions. Since the differential diagnosis in young patients who present with acute urinary retention also includes multiple sclerosis, lumbosacral disk herniation, rheumatological disorders and drug intoxication, a thorough history and careful neurological examination are of paramount importance in distinguishing these syndromes. As part of a directed neurological evaluation prompt performance of lumbar puncture is indicated; a lymphocytic pleocytosis is suggestive of herpetic meningitis. Culture of Herpes simplex virus from the cerebrospinal fluid should be attempted. We recommend conservative management only, typically with intermittent catheterization, since bladder function usually normalizes within 10 to 14 days.

Endoscopic nasobiliary catheter drainage in biliary and pancreatic disease. Nasobiliary catheter drainage was first introduced a decade ago. It provides drainage of the biliary system and facilitates interventional procedures of the biliary and pancreatic system, both for therapy and research purposes. The present review addresses the designs of nasobiliary catheters, the technique of insertion, and indications for drainage, with special emphasis on the management of bile duct stones and associated complications. Its potential application in biliary research is discussed further. Certain caveats in the performance of nasobiliary drainage are also included. All of these emphasize the need for this technique to be included in therapeutic endoscopy training.

A rapid, effective technique for retrograde crossing of valvular aortic stenosis using standard coronary catheters Retrograde crossing of valvular aortic stenosis can be challenging even to experienced angiographers. In 446 of 447 consecutive patients with aortic stenosis catheterized during the past 3 years, a technique using a standard Judkins right coronary catheter and a floppy straight tipped guide wire was successful in rapidly and efficiently crossing these pathologically distorted valves in retrograde fashion. Once the valve was crossed, the coronary catheter was replaced with a pigtail catheter for pressure and ventriculography. The majority of these valves required less than 2 min to cross using this technique. This method is valuable in limiting the time required for catheterization, thus helping to reduce procedure related morbidity in these oftimes critically ill patients.

Recurrent laryngeal nerve avulsion for treatment of spastic dysphonia. Treatment of spastic dysphonia by recurrent laryngeal nerve section has resulted in reproducibly good results in the early postoperative period in most patients. However, critical long-term follow-up has shown a high recurrence rate of adductor spasms by the third year after initial nerve section. A patient who developed recurring adductor spasms 1 year after nerve section was reexplored, with identification of neural regrowth into the distal segment of the recurrent laryngeal nerve. The technique of neural avulsion removing the distal nerve up to its insertion into the laryngeal muscles is described. Neural regrowth, which is just one of the possible mechanisms for recurrence of spastic dysphonia, should be prevented by this surgical modification. Twelve patients who have undergone neural avulsion primarily for spastic dysphonia are being followed up without recurrence of symptoms thus far. Although these results appear promising, this short follow-up that averages 1.5 years must be extended to firmly support these concepts.

Intraluminal pressure adjacent to left colonic anastomoses. A cumulative total of 89 h of pressure data was acquired from both sides of a left colonic anastomosis in 15 patients over a median period of 7 postoperative study days. Patients had a colonic ileus lasting 3-10 days and during this proximal and distal inactivity the intraluminal pressure remained within 6 mmHg of atmospheric pressure. After recovery of activity, pressures proximal to the anastomosis in excess of 10 mmHg occurred during less than 1 per cent of the recording time. Distal peak pressures were significantly elevated with respect to the proximal site (P less than 0.001). Two-thirds of the distal pressures recorded were between 10 and 20 mmHg and 98 per cent were less than 50 mmHg; the peak distal pressure was 90 mmHg. Four patients had distal repetitive tonic contractions creating a pressure difference across the anastomosis with a mean of 20 mmHg and a peak of 45 mmHg. Each contraction persisted for 15-20 min. Intraluminal pressures are unlikely to play a role in anastomotic dehiscence.

Bacterial meningitis: an update. Antibiotics and improvements in supportive care have greatly reduced the mortality from bacterial meningitis. Nevertheless, the incidence of neurodevelopmental sequelae remains unacceptably high. Ampicillin and chloramphenicol remain the standard for antimicrobial therapy against which other agents must be compared. A number of adjunct therapies are being investigated for their possible effectiveness in reducing hearing loss and other neurologic effects of this disease. There continues to be a need for carefully performed follow-up studies to assess any possible benefit of these agents. A significant percentage of children surviving an episode of bacterial meningitis have obvious or subtle neurodevelopmental deficits. The role of the pediatric neurologist should not end with management of acute problems such as seizures but should be expanded to aid in close developmental monitoring of these high-risk children.

Immunophenotypic characteristics of cerebrospinal fluid cells in children with acute lymphoblastic leukemia at diagnosis. The presence of meningeal involvement in children with acute lymphoblastic leukemia (ALL) may have important prognostic and therapeutic implications. Conventional methods of diagnosing central nervous system (CNS) leukemia rely on the interpretation of cerebrospinal fluid (CSF) cell morphology, which may produce ambiguous results in the presence of minimal leukemic involvement. A methodology has been developed for immunophenotyping small numbers of CSF cells while preserving cell morphology. CSF samples from 33 children with CD10 (common ALL antigen [CALLA]) positive ALL were examined at initial presentation using both conventional morphology and this combined immunohistopathologic technique. Six (18%) of the samples contained lymphoblasts or cells considered morphologically suspicious for leukemic involvement. Nine additional samples (27% of the total) had normal CSF morphology, but contained increased numbers of CALLA positive cells. Twelve of the 33 samples were also examined for the simultaneous presence of nuclear terminal deoxynucleotidyl transferase (TdT) and demonstrated increased numbers of cells positive for both TdT and CD10. These data suggest that a large proportion of children with ALL may have abnormalities of CSF cells at initial diagnosis consistent with the presence of occult leukemic involvement.

Phospholipids from rat, human, and canine gastric mucosa. Composition and metabolism of molecular classes of phosphatidylcholine. To validate a recent proposal that a phospholipid lining with a high content of dipalmitoylphosphatidylcholine may protect gastric mucosa against luminal acid, it was decided to study composition and metabolism of phospholipids in the gastric mucosa. Phospholipids were analyzed in rat, human, and dog gastric mucosal surface tissue and in a chloroform/methanol-lavage of rat and canine stomach. Phosphatidylcholine and phosphatidylethanolamine were the main components. Saturated fatty acids were almost exclusively esterified at the sn-1 position of the glycerol moiety of phosphatidylcholine, and unsaturated fatty acids mainly at the sn-2 position. The disaturated class of phosphatidylcholine comprised 2%-6% of total phosphatidylcholine. Precursors of phosphatidylcholine, i.e., [32P]orthophosphate and [methyl-14C]choline, were preferentially incorporated into the disaturated molecular class 0.5-6 hours after IV administration. It can be speculated that disaturated phosphatidylcholine, although quantitatively a minor component, is specifically triggered in mucosal renewal processes.

Importance of sampling method in DNA analysis of lung cancer. Lung carcinomas are characterised by considerable histological variation within the tumour. The possible effects of this morphological heterogeneity on the estimation of tumour ploidy were investigated. Multiple tissue blocks were systematically taken from 20 lung tumours and analysed by flow cytometry. The routine, archival paraffin wax embedded diagnostic blocks from these cases were also analysed. Nineteen (95%) of the tumours were shown to contain aneuploid stemlines by systematic sampling, but if only one of these systematic tissue blocks had been taken from each case the incidence of DNA aneuploidy could have been as low as 45%. Only 15 (75%) tumours were aneuploid when all the routine archival blocks were analysed, but by specifically selecting tumour areas from the archival material the accuracy of this method was increased to 90%. It is concluded that tumour sampling methods are of primary importance in assessing the DNA content of lung tumours. Routine paraffin wax embedded archival tissue provides a suitable source of material for this purpose, provided that "turnover" selection is carried out.

Clinical review 16: Parathyroid hormone-related proteins: coming of age in the 1990s. The last 3 yr have yielded a fertile harvest of new information on the HHM clinical syndrome and on the novel peptide hormone family responsible for the syndrome. Whereas the clinical riddle enshrouding the HHM syndrome first posed in the early 1940s appears to have been largely solved, a whole new field, concerning the physiological role(s) of PTHRP has opened. The field has evolved rapidly and provides an example of fruitful clinical investigation: the original problem was a clinical one (the HHM syndrome); understanding the clinical disorder led to pursuit of the problem in the laboratory (adenylate cyclase assays, protein purification, molecular cloning, PTHRP synthesis); and observations made in the laboratory have rapidly yielded clinical fruits (PTHRP immunoassays) and opened a new window on normal physiology.

Specificity of affective and autonomic symptoms of depression in Parkinson's disease. Previous investigators have suggested that numerous symptoms used to diagnose depression, such as sleep or appetite disturbance, are non-specific in medically ill patients, and alternative diagnostic criteria should be developed. In the study this hypothesis was tested in Parkinson's disease (PD) by comparing patients with PD who reported a depressive mood with patients having PD but without a depressive mood. Depressed patients showed a significantly higher frequency of both autonomic and affective symptoms of depression. Depressed patients with PD reported a significantly higher frequency of worrying, brooding, loss of interest, hopelessness, suicidal tendencies, social withdrawal, self-depreciation, ideas of reference, anxiety symptoms, loss of appetite, initial and middle insomnia, and loss of libido when compared with non-depressed patients. No significant between-group differences, however, were observed in the frequency of anergia, motor retardation, and early morning awakening.

Irritable bowel syndrome in women having diagnostic laparoscopy or hysterectomy. Relation to gynecologic features and outcome. We identified irritable bowel syndrome (IBS) in 47.7% of 86 women having diagnostic laparoscopy for chronic pelvic pain, 39.5% of 172 women having elective hysterectomy, and 32.0% of 172 controls age-matched for the hysterectomy group (P = NS). Constipation and pain subtype IBS were more common in hysterectomy patients than controls (P less than 0.05). In laparoscopy patients, dyspareunia was more common in those with IBS than in those without it (P less than 0.05). In the hysterectomy group, more IBS patients had chronic pelvic pain (P less than 0.005), and abnormal menses (P less than 0.01). Chronic pelvic pain was more frequently the only prehysterectomy diagnosis in IBS patients (P less than 0.05), and IBS was present more often when pain was a reason for hysterectomy (P less than 0.01). One year after laparoscopy, IBS patients gave lower overall status ratings (P less than 0.01) and lower pain improvement ratings (P less than 0.05) than non-IBS patients. In women who had a hysterectomy for pain, there was less pain improvement one year later in those with the pain subtype of IBS than in non-IBS patients (P less than 0.05). IBS is associated with gynecologic symptoms and affects the symptomatic outcome of diagnostic laparoscopy and hysterectomy.

Pulmonary hypertension five years after left pneumonectomy for adenoid cystic carcinoma. We report the findings in a patient with shortness of breath due to pulmonary hypertension five years after left pneumonectomy. Mediastinal recurrence of an incompletely resected and slowly growing adenoid cystic carcinoma of the left main bronchus had encased the right main pulmonary artery.

Cerebral falciparum malaria mimicking thrombotic thrombocytopenic purpura. We have described a patient with cerebral falciparum malaria who had rapidly progressive CNS deterioration, renal failure, hemolytic anemia associated with striking and varied erythrocyte morphologic changes, and thrombocytopenia. The initial diagnosis was thrombotic thrombocytopenic purpura (TTP) of unknown origin. Reexamination of the peripheral smear of this comatose patient led to correct diagnosis and effective treatment in this case of cerebral falciparum malaria--another of medicine's great mimickers.

Endoscopic laser surgery. A single-center comprehensive experience. A retrospective review of endoscopic procedures using the Nd:YAG laser was carried out for patients treated between October 1985 and March 1989. During this 42-month period 165 procedures were performed on 100 patients. The study encompasses a unique period of time in this center, as it includes the initial application, and finally, the time when its use became routine. Indications for laser surgery included the treatment of tumors, bleeding, benign strictures, arterial occlusions, and hemorrhoids. Nd:YAG laser was found to be effective in the treatment of these lesions. The overall success rate was 81 per cent. Patients who are poor surgical candidates would especially benefit from this therapeutic alternative.

Islet cell carcinoma of the pancreas presenting as bleeding from isolated gastric varices. Report of a case and review of the literature. Gastrointestinal hemorrhage from left-sided portal hypertension and gastric varices is an unusual presentation for islet cell carcinoma of the pancreas. Islet cell tumors of the pancreas themselves are rare. They present in a variety of ways. Those that elaborate functional hormones cause specific neuroendocrine syndromes. Nonfunctional tumors characteristically present later with symptoms of metastatic disease or as a result of local enlargement. We present a case of islet cell carcinoma of the pancreas presenting with recurrent gastrointestinal bleeding from gastric varices and review the literature for this rare presentation. We emphasize the importance of a careful initial diagnostic work-up that may enable curative surgery.

Young-onset Parkinson's disease: a clinical review. Young-onset Parkinson's disease (YOPD) is arbitrarily defined as that which produces initial symptoms between the ages of 21 and 39, inclusive. The special problems and concerns of the patient with YOPD present as much of a challenge and opportunity for the clinician as the disease itself does for the researcher. In contrast to juvenile parkinsonism, which is a heterogeneous group of clinicopathologic entities presenting (also arbitrarily) before age 21, YOPD appears to be the same nosologic entity as older-onset PD. It comprises approximately 5% of referral populations in Western countries and about 10% in Japan. Its annual incidence relative to the population at risk is about 1/10 that of PD at age sixty. YOPD tends to have more gradual progression of parkinsonian signs and symptoms, earlier appearance of levodopa-related dyskinesias and levodopa-dose-related motor fluctuations, and frequent presence of dystonia as an early or presenting sign. Studies conflict with regard to the suspected greater familial frequency and lesser frequency of dementia than in older-onset PD.

Transoesophageal echocardiography improves the diagnostic value of cardiac ultrasound in patients with carcinoid heart disease. Transthoracic and transoesophageal cardiac echocardiography and Doppler investigations were performed in 31 consecutive patients with malignant midgut carcinoid tumours. The transoesophageal images allowed measurement of the thickness of the atrioventricular valve leaflets and the superficial wall layers on the cavity side of both atria. The mean thickness of the anterior tricuspid leaflet was significantly greater than that of the mitral valve--a difference not seen in a control group of age-matched patients without carcinoid tumours and with normal cardiac ultrasound findings. In addition, the edges of the tricuspid leaflets were thickened giving them a clubbed appearance. Tricuspid incompetence was detected transoesophageally in 71% of the patients with carcinoid compared with 57% by transthoracic investigation. The inner layer of the right atrial wall in the carcinoid patients was significantly thicker than that of the left atrium and that of both atria in the controls. Furthermore, patients with other signs of severe carcinoid heart disease had significantly thicker mean right atrial luminal wall layer than those with less or no signs of right heart disease. Transoesophageal cardiac ultrasound investigation improved the diagnostic accuracy and seemed to show the structural changes typical of carcinoid heart disease established by histopathological investigations.

Unusual complication of an ingested foreign body. Migration of a foreign body from the mouth and throat to the subcutaneous tissue of the neck is very rare. We present a case of a migrating foreign body (a piece of straw) from the floor of the mouth to the neck. To our knowledge, this is the second case reported in the English literature.

Smoking cessation in chronic Reinke's oedema. In evaluating the long term results of surgical treatment of Reinke's oedema, there has been found to be a high incidence of recurrence. The recurrence rate is significantly lower amongst those patients who gave up smoking after treatment. A group of patients with chronic Reinke's oedema were followed for six months. Maximum efforts were made to help the patients to stop smoking. Twenty-nine patients entered the study, but only eight of them (28 per cent) refrained from smoking; all were women (39-70 years) and all experienced reduced discomfort, although none of the voices were restored to normal. Diffuse laryngitis disappeared completely, but the oedema did not disappear entirely in any patient. Before treatment of chronic Reinke's oedema patients must be well advised and informed, and if surgery is decided upon, they must be urged most strongly to stop smoking, if they wish to enhance the possibility of satisfactory long-term results.

Infantile acute hemorrhagic edema of the skin: study of ten cases. Infantile acute hemorrhagic edema of the skin is not included as a separate entity in the current English-language literature as it is in continental Europe. Therefore we have attempted to clarify the nosologic position of acute hemorrhagic edema among cutaneous vasculitides in children, on the basis of our experience in 10 cases. Our study confirms that acute hemorrhagic edema affects infants between 4 and 24 months of age. The two main features are an ecchymotic purpura, often in a cockade pattern, and an inflammatory edema of the limbs and face. Visceral involvement is uncommon. Spontaneous and complete resolution occurs within 1 to 3 weeks; one to four attacks may occur. Histopathologic examination demonstrates a leukocytoclastic vasculitis. Perivascular IgA deposits can occasionally be found. Besides typical acute hemorrhagic edema, some cases in 2- to 4-year-old children appear to overlap with Schonlein-Henoch purpura. We suggest that typical acute hemorrhagic edema should be regarded as a separate clinical entity. This allows an appropriate prognosis to be made for this generally benign disease of infants.

Insulin-like growth factor-I receptors in human hyperplastic prostate tissue: characterization, tissue localization, and their modulation by chronic treatment with a gonadotropin-releasing hormone analog. Insulin-like growth factor I (IGF-I) receptors were characterized in membranes obtained from prostate tissue of patients affected by benign prostatic hyperplasia (BPH) before and after treatment with a GnRH agonist analog. Binding of [125I]IGF-I to membranes obtained from untreated patients was specific and time and temperature dependent. Analysis of the binding data yielded two classes of binding sites, one of high affinity (Kd, 10(-11) mol/L) and one of lower affinity (Kd, 10(-9) mol/L). BPH membrane preparations were affinity-cross linked to labeled IGF-I, and then subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis by autoradiography revealed one labeled protein with an apparent Mr = 300K under nonreducing conditions and two labeled protein with Mr = 270K and Mr = 130K under reducing conditions. Excess unlabeled IGF-II reduce both of them, whereas the same excess of IGF-I completely abolished them. In membrane preparations of prostatic tissues from patients affected by BPH and treated for 2 months with a GnRH agonist analog, the binding capacities of both binding sites were significantly higher than those of BPH tissue from untreated patients, whereas binding affinities were unchanged. The IGF-I receptor in BPH prostate tissue of untreated patients was mainly localized in the basal layer of the epithelium, as demonstrated by immunohistochemical staining, whereas in the tissue from treated patients positive staining was found also in the glandular epithelium. These results demonstrate that: 1) specific binding sites for IGF-I are present in prostatic tissue from patients with BPH, 2) androgen deprivation increases their binding capacities and seems to modify their epithelial localization.

Isolated lung transplantation for pulmonary fibrosis. The peri-operative anaesthetic management of 11 patients with pulmonary fibrosis undergoing single-lung transplantation is presented. Intra-operative problems, the early postoperative phase of recovery and intensive care, and other incidents in which general anaesthesia was required for the management of complications, are featured. Results, both short- and long-term, are mentioned. Major intra-operative events that cause concern appear to be related to the severity of the presenting illness and the development of respiratory failure. Others have reported the development of intra-operative cardiac failure. All cases were successfully managed operatively using conventional one-lung anaesthesia, although resort to partial cardiopulmonary bypass may have been indicated in some. The indications and attitudes to utilising cardiopulmonary bypass in the evolution of techniques for facilitating single-lung transplantation are reviewed.

Nephron function in the early phase of ischemic renal failure. Significance of erythrocyte trapping. Trapping of red blood cells (RBCs) in renal medulla vasculature in postischemic acute renal failure (ARF) was found to depend upon the length of the ischemic period. Thus trapping occurred after 45 minutes but not 25 minutes of ischemia. By prior hemodilution to a hematocrit (hct) of 30%, RBC trapping after 45 minutes of ischemia could be completely prevented. Likewise hemo-concentration (hct = 60%) before 25 minutes of ischemia resulted in extensive RBC trapping. By increasing or decreasing the hct, the contribution of RBC trapping to the functional defects and decrease in renal blood flow that follows minor (25 min) and more substantial (45 min) ischemia was investigated. Renal blood flow (RBF) was measured by microspheres, and vascular and tubular pressure by the micropuncture technique. Glomerular filtration rate (GFR) was estimated from inulin clearance, and tubular function from urine osmolality and sodium and potassium excretion. It was found that postischemic RBF was not correlated to RBC trapping but depended on the length of ischemia. After both 25 and 45 minutes of ischemia tubular obstructions occurred in the proximal tubules and/or loops of Henle, causing an increase in proximal tubular pressure. These obstructions were dependent on the length of ischemia but not on RBC trapping. After hemoconcentration and 25 minutes of ischemia there was an increment in distal tubular pressure, indicating that abundant RBC trapping may contribute to an increase in tubular pressure by compression of medullary tubules and thereby reduce GFR. When the damage was more severe other factors came into play and the contribution of RBC trapping to the decrease in GFR was minimal.

Determinants of the ventricular rate during atrial fibrillation. Determinants of the ventricular cycle length during atrial fibrillation were examined in 52 patients. Thirty-three patients had structural heart disease and none had an accessory atrioventricular (AV) connection. The AV node effective and functional refractory periods, the shortest atrial pacing cycle length associated with 1:1 conduction, the AV node conduction time and indexes of concealed conduction in the AV node were measured in the baseline state (36 patients) and after modification of sympathetic tone by infusion of isoproterenol or propranolol (8 patients each). Atrial fibrillation was then induced with rapid atrial pacing, and the mean, shortest and longest ventricular cycle lengths were measured. Variables that correlated most strongly with the mean RR interval during atrial fibrillation were the AV node effective refractory period (r = 0.93; p less than 0.001), AV node functional refractory period (r = 0.87; p less than 0.001) and shortest atrial pacing cycle length associated with 1:1 conduction (r = 0.91; p less than 0.001). The AH interval during sinus rhythm (r = 0.74; p less than 0.001) and during atrial pacing at the shortest cycle length with 1:1 conduction (r = 0.52; p less than 0.001) had weaker correlations. Measures of concealed conduction did not improve the prediction of the mean or longest ventricular cycle length during atrial fibrillation. In conclusion, the refractory periods and conductivity of the AV node are the best indicators of the potential of the node to transmit atrial impulses to the ventricles during atrial fibrillation. The degree of concealed conduction in the AV node is a less important determinant of the mean ventricular rate during atrial fibrillation.

Left ventricular diastolic function in patients with left ventricular systolic dysfunction due to coronary artery disease and effect of nicardipine. To assess the effect of nicardipine on left ventricular (LV) diastolic function independent of concurrent effects on loading conditions in patients with LV systolic dysfunction due to coronary artery disease, equihypotensive doses of intravenous nitroprusside and nicardipine were administered to 12 patients with congestive heart failure due to previous myocardial infarction (LV ejection fraction less than 0.40). LV micromanometer pressure and simultaneous radionuclide volume were obtained during a baseline period, during nitroprusside infusion, during a second baseline period and during nicardipine infusion. Mean systemic arterial pressure decreased an average of 21 mm Hg with nitroprusside and 19 mm Hg with nicardipine. A greater decrease in LV end-diastolic pressure was observed with nitroprusside (29 +/- 2 to 15 +/- 2 mm Hg, p less than 0.01) than with nicardipine (29 +/- 2 to 25 +/- 3 mm Hg, p less than 0.05). There was a decrease in the time constant of relaxation during nitroprusside but not during nicardipine infusion. There was enough overlap in LV volumes in the baseline and nitroprusside periods to compare diastolic pressure-volume relations over a common range of volumes in 4 patients, and enough overlap in the baseline and nicardipine periods in 11 patients. The relation was shifted downward in 3 of 4 patients taking nitroprusside and in 6 of 11 patients taking nicardipine. The relation between end-diastolic pressure and volume was not shifted with nicardipine.