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Delayed facial palsy following uncomplicated stapedectomy. We report six cases of partial lower motor neurone facial palsy occurring between four and ten days after uncomplicated stapedectomy. The aetiology is unclear but recovery was rapid and complete in all patients.

Acute cholangitis. Cholangitis is an infection of the biliary ductal system that results from the combination of bactibilia and biliary obstruction. Choledocholithiasis has been the leading cause of cholangitis. However, in recent years, especially at tertiary referral centers, nonoperative biliary manipulations, often in patients with unresectable malignancies, have become the most common cause of cholangitis. As a result, the complete triad of fever and chills, jaundice, and abdominal pain, as originally described by Charcot, is now seen less frequently. Most patients still have leukocytosis and abnormal liver function tests, but many patients with indwelling tubes may develop cholangitis without significant jaundice. E. coli, Klebsiella species, and the enterococci remain the most frequently isolated organisms, and anaerobes including Bacteroides fragilis are recovered in 15% to 30% of patients. However, Enterobacter and Pseudomonas species, as well as yeasts, are now being isolated more frequently from patients with indwelling tubes, who often have been treated previously with antibiotics. Computed cholangiography usually is necessary to determine the cause and site of biliary obstruction. In the majority of patients with cholangitis, cholangiography can be delayed until the patient has been afebrile for a minimum of 24 to 48 hours. Initial therapy includes bowel rest, intravenous fluids, and antibiotics. Many antibiotic regimens are now available to cover the gram-negative aerobes, the enterococcus, and the anaerobes that are likely to be causing the biliary infection. The combination of a penicillin and an aminoglycoside has been the gold standard. However, recent studies suggest that the newer broad-spectrum penicillins provide adequate therapy for these patients. Only a small percentage (5%-10%) of patients with toxic cholangitis require emergency biliary decompression. The choice of percutaneous or endoscopic drainage should be made on the basis of the presumed site and cause of obstruction as well as local expertise. The nature of the biliary obstruction may be the most important determinant of outcome. At present, patients with end-stage malignant obstruction account for most of the deaths, whereas approximately 95% of patients survive an episode of cholangitis.

Child care practices with respect to acute respiratory tract infection in a poor, urban community in Nigeria. A longitudinal study conducted over a 3-year period in a poor, urban community in Nigeria, a developing country, found that acute respiratory tract infection (ARI) was common, in particular among infants and boys. Between 81% and 95% of the children treated for ARI over the 3-year period were brought to the clinic by their mothers. About 32% of these children had been treated with cough medicines, 42% with antipyretics, 5% with antibiotics, and 10% with hematinics before they were brought to the clinic. The source of such medications included medicines left over from previous prescriptions and those bought from chemists' shops and street vendors. Up to 64% of the children treated for ARI had been force-fed local herbal teas by their mothers; herbal teas were used for both preventive and curative purposes.

Levamisole and 5-fluorouracil therapy for resected colon cancer: a new indication. OBJECTIVE: To evaluate the benefits and risks of postoperative treatment with levamisole plus 5-fluorouracil (5-FU) in patients with colon cancer. DESIGN: Computerized searches of MEDLINE and CANCERLIT were performed, and the reference list of each retrieved article was checked. Only randomized trials of therapy with levamisole alone or combined with 5-FU for colon cancer without distant metastases were included. The studies were then evaluated with the use of four criteria. RESULTS: We reviewed six randomized trials, of which three satisfied our criteria. Two studies demonstrated a significant improvement in the survival rate with levamisole plus 5-FU among patients with colon cancer and pathologically confirmed metastases to adjacent lymph nodes (Dukes' stage C). A subgroup analysis in another study demonstrated a similar benefit. The toxic effects of the drugs were generally mild. The three other studies showed no difference in survival rates between the treatment groups; however, the samples were too small to detect a clinically or statistically important difference. CONCLUSIONS: Because many patients with colon cancer will suffer a relapse we recommend that they be offered the opportunity to participate in clinical trials of adjuvant therapy. For those with stage C disease not entering a clinical trial levamisole plus 5-FU is appropriate adjuvant therapy.

Acute aluminum toxicity after continuous intravesical alum irrigation for hemorrhagic cystitis. An encephalopathy and cardiomyopathy developed in a seventeen-year-old girl with chemotherapy-induced renal failure while receiving an intravesical aluminum infusion for hemorrhagic cystitis. Premortem serum and postmortem tissue aluminum levels were markedly elevated. It is likely that her inability to excrete absorbed aluminum contributed to her death. Aluminum infusions should be used with caution in patients with renal failure.

Diagnosis and management of familial dyslipoproteinemia in children and adolescents. CAD results from atherosclerosis, a chronic disease process that has its origin in childhood. Children and adolescents can be at higher risk for CAD by virtue of being from families with premature CAD or familial dyslipoproteinemias. The plasma lipid and lipoprotein levels result from a number of complex metabolic processes that are under the control of genetic and environmental (e.g., diet) influences. The normal ranges of plasma lipids and lipoproteins in children are known, and children and adolescents with dyslipoproteinemia are ordinarily defined as those having levels of plasma total, LDL, or triglyceride above the 95th percentile or with a low HDL cholesterol below the 5th percentile. Children of a parent with documented dyslipoproteinemia or with family history of premature CAD may be screened in the fasting state any time after 2 years of age. Following the exclusion of secondary causes of dyslipoproteinemia, the diagnosis of primary dyslipoproteinemia can be made. Lipoprotein patterns are not diagnostic for a given genotype. Efforts to determine further the biochemical defects responsible for a given phenotype have led to the investigation of gene coding for the apolipoproteins, the key enzymes in the lipoproteins pathways (LPL, HDL, and LCAT) and the receptors that process lipoproteins, such as the LDL receptor and the chylomicron remnant receptor. From a practical standpoint, the diagnosis of the kind of dyslipoproteinemia in a child will depend upon the nature and severity of the dyslipoproteinemia, both in the child (or adolescent) and in parents and siblings. Marked increases in plasma total and LDL cholesterol in the child and in at least one of the parents often reflect the presence of familial hypercholesterolemia, an inherited dominant condition due to a defect in the LDL receptor gene. The triglyceride levels are often normal. If the child has a different dyslipoproteinemia pattern from siblings and parents, then the diagnosis of familial combined hyperlipidemia or hyperapobetalipoproteinemia should be considered. Most children with mild or borderline elevations in total and LDL cholesterol will have polygenic hypercholesterolemia. Triglyceride problems in children and adolescents are relatively uncommon, particularly the more severe hypertriglyceridemia such as that found in lipoprotein lipase and apoC-II deficiency, dysbetalipoproteinemia, and type V hyperlipoproteinemia. High levels of Lp(a) lipoprotein, in isolation or in combination with other dyslipoproteinemia, accelerate risk for CAD. Low levels of HDL cholesterol in the absence of other abnormalities suggest the diagnosis of hypoalphalipoproteinemia.(ABSTRACT TRUNCATED AT 400 WORDS).

Immunodominant regions for T helper-cell sensitization on the human nicotinic receptor alpha subunit in myasthenia gravis. In myasthenia gravis an autoimmune response against the nicotinic acetylcholine receptor (AChR) occurs. The alpha subunit of the AChR contains both the epitope(s) that dominates the antibody response (main immunogenic region) and epitopes involved in T helper cell sensitization. In this study, overlapping synthetic peptides corresponding to the complete AChR alpha-subunit sequence were used to propagate polyclonal AChR-specific T helper cell lines from four myasthenic patients of different HLA types. Response of the T helper lines to the individual peptides was studied. Four immunodominant sequence segments were identified--i.e., residues 48-67, 101-120, 304-322, and 419-437. These regions did not include residues known to form the main immunogenic region or the cholinergic binding site, and they frequently contained sequence motifs that have been proposed to be related to T-epitope formation.

Evaluation of current extrication orthoses in immobilization of the unstable cervical spine. An experiment was designed to evaluate the comparative stabilizing efficacy of several widely used semi-rigid orthoses applied to unstable fresh cadaver cervical spines subject to load. Cadaver specimens were surgically destabilized at the C4-5 segment. Lateral radiographs of the destabilized spine were obtained before and after collar placement and after the application of a 5-pound flexion force. Data analysis employing a one-way analysis of variance showed no statistically significant difference in the Necloc's, Philadelphia Collar's, or the Stifneck's ability to stabilize the cervical spine against a deforming flexion force (P greater than 0.05). They all provide translational stability while allowing angular changes to occur with application of the flexion force. The Philadelphia Collar Halo System is statistically superior to all three of the aforementioned collars in prevention of both translation and sagittal rotation (P less than 0.05).

Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (the CASCADE study). This randomized study evaluates survivors of out-of-hospital ventricular fibrillation (VF) not associated with a Q-wave acute myocardial infarction who are deemed to be at a high risk of recurrence of VF. It compares the outcome of treatment with empirically administered amiodarone with the outcome of treatment with other antiarrhythmic agents guided by electrophysiologic testing or Holter recording, or both. The goal of therapy guided by electrophysiologic testing is to suppress inducible ventricular tachycardia (VT) or VF. Holter recording is used as the primary means of adjusting therapy only if patients are noninducible at the baseline electrophysiologic study. Patients are stratified according to cardiac diagnosis, ejection fraction, and whether they had previously received an antiarrhythmic agent that failed to suppress their arrhythmias. The primary end point of the study is total cardiac mortality. The first patient was enrolled in a pilot study on April 26, 1984. By October 1988, 142 patients had been enrolled in the full study and, as of May 1990, 199 patients have been enrolled. Compliance with therapy has been good, with no patients lost to follow-up and 8% of patients, equal in both drug groups, crossing over to alternate therapy. Baseline clinical characteristics remain similar in amiodarone and conventional drug groups. Pulmonary toxicity with amiodarone is 7% at 1 year, with no patients dying of pulmonary toxicity. In the first 142 patients, the overall 1-year cardiac mortality was 19%, with a 17% arrhythmic mortality (either VF or presumed arrhythmic death).

Risk for postoperative congestive heart failure. To identify predictors of postoperative congestive heart failure (CHF), a high-risk population, mainly hypertensive and diabetic patients undergoing elective general operations, was studied. Of the 254 patients, 6 per cent had postoperative CHF. Among patients with preoperative cardiac disease (that is, previous myocardial infarction, valvular disease or CHF), 17 per cent had postoperative CHF; in contrast with less than 1 per cent of those without cardiac disease (p less than 0.001). Patients with diabetes were also at high risk (12 versus 2 per cent, p less than 0.005), particularly those with cardiac disease. Patients who had equal to or greater than 40 millimeters of mercury increases or decreases intraoperatively in mean arterial pressure in relation to preoperative baseline had increased postoperative failure rates (p less than 0.02). Of note, postoperative failure rates were highest among patients with less than 500 milliliters per hour of net intake (input and output) (p less than 0.03). Risk for postoperative CHF was restricted to patients with preoperative symptomatic cardiac disease and was especially high if patients also had diabetes. Intraoperative fluctuations in mean arterial pressure increased the probability of postoperative failure, while the intraoperative administration of higher net volumes of fluid was associated with decreased risk.

Doxazosin therapy in the treatment of diabetic hypertension. The incidence of cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM) has not been reduced by the control of hyperglycemia alone. Hypertension and dyslipidemia may be the major determinants of macrovascular disease in these patients. With the high prevalence of hypertension in NIDDM, antihypertensive drugs are likely to be important determinants of an atherogenic lipid profile. To date, there is no completed major randomized controlled trial of antihypertensive treatment outcome in a diabetic population, and as such, drug choice for the treatment of diabetic hypertension is often based on evidence extrapolated from studies in nondiabetic groups. However, two short-term studies have assessed the effects of doxazosin antihypertensive therapy in subjects with NIDDM. Both studies showed that the significant reduction in blood pressure with doxazosin treatment was associated with favorable effects on the serum lipid profile. In one study, contrasting adverse effects of atenolol treatment on glycemic control, lipids, and lipoproteins were observed. Doxazosin therapy was associated with a trend toward correcting the disturbances of lipoprotein metabolism characteristic of NIDDM. These metabolic effects, combined with effective lowering of blood pressure by doxazosin, may be important determinants of cardiovascular disease in the long term.

Pyloric deformation from peptic disease. Radiographic evidence for incompetence rather than obstruction. We have used double-contrast radiographic techniques to clarify what changes in the configuration and movements of the gastroduodenal junction result when peptic lesions involve the distal gastric segment between the proximal (PPL) and the distal pyloric muscle loop (DPL). Among 50 cases of pyloric ulceration diagnosed during a four-year study period, 18 cases fulfilled all study criteria. Ulcers maintained a consistent location with regard to the muscular structures of the pylorus, and by affecting these structures, led to many strange deformations of the gastric outlet including permanent pseudodiverticula and reversal of pyloric angulation. The most common site for peptic lesions in the pyloric segment was the protuberance of the lesser curvature called the pyloric torus; many torus lesions extended into and destroyed the DPL. This led to widening of the gastric outlet and radiographic evidence of increased duodenogastric reflux. Pyloric closure was further impaired in this setting because the mucosa no longer prolapsed into the gastric outlet and did not occlude the pyloric lumen as it normally does. Less common lesions involved the greater curvature and the PPL. In one patient, scarring of the PPL led to an antral web and gastric hyperperistalsis. This was the only patient who required operation for chronic gastric outlet obstruction. One-third of the 18 patients had reflux esophagitis in addition to peptic pyloric disease. In most patients without additional ulcerogenic risk factors, treatment with antisecretory agents led to the healing of ulcer craters. We conclude that the morphologic and functional changes of the gastric outlet caused by peptic lesions depend, in part, on the effect the ulcer has on the underlying pyloric musculature.

Routes and incidence of communication of lumbar discs with surrounding neural structures. Several authors have previously reported the complications resulting from contact between a diagnostic or therapeutic agent injected into an intervertebral disc and neural tissue. This study was undertaken to demonstrate the common routes by which, and frequency with which this contact occurs. Of 105 cadaveric intervertebral discs studies, 15 (14%) leaked. Of the discs that leaked, 27% demonstrated contact of injected dye with the adjacent spinal nerve. The high rate of leakage may be related to the age of the cadavers. Nonetheless, the contact between substances injected into an intervertebral disc and adjacent neural tissue during discography offers an alternate mechanism of pain reproduction in an incompetent disc. It also suggests that nontoxic agents should be used for discography and that intervertebral discs should be proved competent before chemonucleolysis.

The need for quality assurance in vascular surgery. The need for quality assurance in vascular surgery can be deduced from the variability in unruptured abdominal aneurysm operative death rates in a group of patients large enough that factors influencing mortality rates other than quality of care can be controlled. Operative mortality rate for 3570 patients undergoing unruptured abdominal aortic aneurysm repair was determined for all non-Veterans Administration surgeons and hospitals in New York State from 1985 to 1987. The average annual number of aneurysm operations per surgeon was 3.6, and per hospital it was 10.2. Unruptured aneurysm repair mortality for surgeons performing 1 to 5 aneurysm operations per year was 10% whereas for surgeons performing more than 26 aneurysm operations per year it was 6% (p less than 0.0001). Unruptured aneurysm repair mortality for hospitals performing 1 to 5 aneurysm operations per year was 14% and for hospitals performing more than 38 aneurysm operations per year it was 5% (p less than 0.0001). Even when these mortality rates were adjusted for differences in patient age, severity of illness, secondary diagnoses and admission status, significant mortality rate differences persisted: 9% versus 4% for low and high volume surgeons, respectively (p less than 0.001), and 12% versus 5% for low and high volume hospitals, respectively (p less than 0.001). Surgeons who performed more than 7 aneurysm operations per year devoted more of their practice to aortic (11%) and vascular operations (52%) than did surgeons who performed 7 or fewer aneurysm operations per year (2% and 19%, respectively).

Cemented total knee arthroplasty for gonarthrosis in patients 55 years old or younger. The results of 68 cemented total knee arthroplasties (TKAs) in 50 patients with gonarthrosis who were 55 years old or younger at the time of surgery were reviewed. These patients were operated on between 1979 and 1987 and were followed for an average of 6.2 years. The average age of the patients was 50 years. Patients were evaluated by the Hospital for Special Surgery knee score. The average preoperative score was 53, and the average follow-up score was 90. Overall, 55 TKAs were rated as excellent and 13 as good. Using the knee rating score advocated by the Knee Society, the average postoperative score was 92 for pain and 84 for function. There were four successful reoperations for patellar component loosening, all in metal-backed patellae. The femoral and tibial components in these patients were intact, and at the follow-up period, two knees were rated as excellent and two as good. Detailed roentgenographic evaluation demonstrated that 20% of tibial components had radiolucencies in at least one zone on the anteroposterior roentgenogram and in 11% on the lateral roentgenogram. Femoral radiolucencies occurred in only 2% of knees. Patellar radiolucencies in one or more zones occurred in 20% of knees that had not had patellar revision. No complete or progressive radiolucencies at the bone-cement interface were noted for any component, and no components were considered to be roentgenographically loose. Cemented TKAs can achieve excellent long-term results in patients younger than 55 years old with gonarthrosis of the knee. These results compare with those obtained in published reports on older age groups.

Parental presence during procedures in an emergency room: results from 50 observations. This report describes the physician-parent-child encounter during an invasive medical procedure in a pediatric emergency department. Fifty children underwent venipuncture or intravenous cannulation performed by 22 physicians and 6 nurses. The median age of the children was 12 months. Parents remained with their children during 31 (62%) of the 50 procedures. Parents were more likely to stay if they had previously stayed when this child (P = .05) or another (P = .02) had undergone a procedure. Parental decision to stay was not related to parental age, gender, race, marital status, or level of education, nor to the residents' age, gender, or level of training. Only 43% of the parents who did stay were given that option by the residents, and of those who did not stay 37% reported that physicians asked them to leave. Nonverbal cues by the residents, such as pulling the curtain closed or turning their back toward parents, were noted in 58% of the encounters in which parents did not stay. The residents and nurses indicated that parents should stay with their child for the following procedures: laceration repair, 66%; venipuncture, 58%; intravenous cannulation, 48%; arterial blood sampling, 32%; suprapubic aspiration, 20%; and lumbar puncture, 14%. In the emergency room studied, it appears that for venipuncture and intravenous cannulation, the majority of parents stay with their children. Parental decision to stay or leave is frequently made without discussion with the physician.

Albumin absorption and protein secretion by the gallbladder in man and in the pig. To study albumin absorption by the gallbladder in man, an in vitro model was first established in the pig and compared with in vivo function in the same species. Water and electrolyte transport and 125I-albumin absorption and protein secretion in vivo and in vitro were compared. Then similar in vitro studies were performed on human gallbladders obtained at surgery. The in vivo study in the pig was performed without disturbing the gallbladder except to tie a cannula in the cystic duct end. The in vitro model was identical in the pig and human gallbladders. Gallbladders were excised using a technique causing minimal injury and anoxia. They were oxygenated on both mucosal and serosal surfaces in a temperature-controlled environment. Luminal and external bath test solutions consisted of modified Ringers bicarbonate with added glucose; luminal solutions also contained 125I-albumin from different species, depending on the study. Active absorption of sodium and water occurred in both types of studies in the pig but in vivo absorption rates were considerably greater than in vitro rates. Albumin absorption in vivo was substantial; although present in vitro, the absorption of albumin was diminished relatively more than electrolyte transport rates. Protein secretion rates into the gallbladder were similar in vitro and in vivo. The results of studies in the human gallbladders in vitro were similar to the pig, except albumin absorption was greater. Some human gallbladders were obtained from control patients and some from patients with cholesterol gallstones. There were no significant differences between the two groups for any of the variables studied; however, the numbers were small and some control gallbladders were not normal gallbladders.

Trends in conserving treatment of invasive carcinoma of the breast in females. This population-based study presents trends in the treatment of node-negative invasive carcinoma of the breast in females during the 1980s in the Detroit metropolitan area. It was done to determine whether or not there has been a significant shift toward conservation of the breast from 1980 to 1987. Trend analyses of surgical treatment, tumor size, node status, year of diagnosis, age and race were performed for 13,217 patients drawn from the Metropolitan Detroit Cancer Surveillance System. A significant increase in the use of conserving the breast was observed, with younger women receiving this treatment option more often than older women. Implications for a continuing shift in the biologic findings and treatment of carcinoma of the breast are discussed.

Improved molecular diagnostics for ornithine transcarbamylase deficiency. Since the cloning of the cDNA for X-linked ornithine transcarbamylase (OTC) in 1984, diagnostic accuracy of OTC deficiency for prenatal and carrier detection has been greatly improved by the use of linkage analysis. However, the use of RFLP-based diagnosis is limited in this and in other new mutation diseases. Here we report both the use of direct mutation detection by new PCR-based techniques and our experience with linkage-based diagnosis in 18 families. We have previously reported the use of chemical mismatch cleavage to detect mutations first in amplified mRNA and then in genomic DNA of patients. This technique has now been utilized for prenatal diagnosis. Primers for specific amplification of OTC exons 1, 3, 5, 9, and 10 have been developed and been employed to map deletions of the OTC gene in two families. These primers also have been used to detect alterations in the TaqI sites found in exons 1, 3, 5, and 9. Four novel mutations of the OTC gene leading to abolition of a TaqI site in the OTC cDNA were discovered. One of these mutations is in exon 1; two lie in exon 3; and one is in exon 9. In addition, we have used the PCR products as probes to identify the exon-specific bands seen on Southern blots and to map the polymorphic BamHI and MspI sites, which are commonly used for linkage analysis. This information will facilitate the interpretation of altered band patterns seen in deletion cases and in cases of point mutations affecting restriction sites. Utilization of the appropriate combination of these molecular techniques permitted accurate diagnostic evaluations in 17 of 18 families.

Genetic differences in susceptibility to glomerular sclerosis: a role for lipids? To better understand the pathogenesis of focal and segmental glomerular hyalinosis and sclerosis (FSGHS), a variety of animal models have been developed--mainly in rats--that allow a comprehensive study of all variables involved, such as hemodynamic, genetic, and metabolic factors. In this article, we briefly review the role of lipids in the pathogenesis of FSGHS and provide evidence that "atherosclerosis of the glomerular mesangium" contributes to the ultimate histopathologic lesion of FSGHS in susceptible rat strains. Observations in a FSGHS-resistant strain revealed several characteristic features that may protect these rats against chronic renal disease such as high nephron numbers, glomerular visceral epithelial cells with a remarkable resistance to toxic injury, minimal sequestration of serum proteins and cholesterol from the circulation into the mesangium, and a remarkable lipoprotein profile in normal as well as nephrotic states with a very low cholesterol content of the very-low-density and low-density lipoprotein fractions. Recent clinicopathologic studies also indicate a correlation between hyperlipidemia and the progression of renal disease. The concept of lipid-mediated glomerular injury warrants further study.

Progression of human papillomavirus type 18-immortalized human keratinocytes to a malignant phenotype. We have developed a model system for progression of human epithelial cells to malignancy, using a human papillomavirus type 18 (HPV-18)-immortalized human keratinocyte cell line. Cells of cell line FEP-1811 were nontumorigenic in athymic mice through at least 12 passages in culture, but after 32 passages were weakly tumorigenic, producing tumors that regressed. After 62 passages they produced invasive squamous cell carcinomas that grew progressively. The progression to malignancy was associated with an increase in the efficiency of forming colonies in soft agar and with altered differentiation properties. In an organotypic culture system, FEP-1811 cells at passages 12 and 32 exhibited features typical of premalignant intraepithelial neoplasia in vivo, and cells at passage 68 exhibited features consistent with squamous cell carcinomas. No change in copy number of the transfected HPV-18 genome or in the level of expression of the viral transforming gene products E6 and E7 was detected between tumorigenic and nontumorigenic cells. Cytogenetic analysis of cells at early, middle, and late passage levels and cells cultured from tumors revealed that several chromosomal abnormalities segregated with the tumorigenic cell populations.

Visuospatial impairment in Parkinson's disease. We explored the nature of the visuospatial deficit in Parkinson's disease (PD) and its progression as a function of disease duration. We compared the performance of 183 patients with idiopathic PD and 90 control subjects matched for age and education on six visuospatial measures. We divided patients into three groups according to the disease duration: early (1 to 4 years), middle (5 to 10 years), and advanced (greater than 10 years). Performance deteriorated in five of the six visuospatial measures, as a function of disease duration. However, the pattern of visuospatial decline depended on whether dementia was present. The results were not influenced by age or anticholinergic medication. These findings support the presence of visuospatial deficits in PD patients, with a changing pattern of impairment related to dementia and progression of the disease.

Factor XIII deficiency and intracranial hemorrhages in infancy. We report an infant with Factor XIII deficiency who had 2 seemingly spontaneous intracranial hemorrhages. It is important to consider Factor XIII deficiency as a possible cause of unexplained intracranial hemorrhages in infancy. Ongoing factor replacement therapy is recommended to prevent further bleeding episodes.

Role of endothelium-derived nitric oxide in the bleeding tendency of uremia. Endothelium-derived relaxing factor, now identified as nitric oxide (NO), is a labile humoral agent formed by vascular endothelial cells from L-arginine. NO mediates the action of substances that induce endothelium-dependent relaxation and plays a role in regulating blood pressure. In this study we investigated whether NO is involved in the pathogenesis of the bleeding tendency associated with renal failure. Rats with extensive surgical ablation of renal mass develop renal insufficiency due to progressive glomerulosclerosis. Like uremic humans, rats with renal mass reduction and uremia have a bleeding tendency that manifests itself by a prolonged bleeding time. We found that N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO formation from L-arginine, completely normalized bleeding time when given to uremic rats. L-NMMA injection also increased ex vivo platelet adhesion but did not affect ex vivo platelet aggregation induced by adenosine diphosphate, arachidonic acid, and calcium ionophore A23187. The shortening effect of L-NMMA on bleeding time was completely reversed by giving the animals the NO precursor L-arginine, but not D-arginine, which is not a precursor of NO. It thus appears that NO is a mediator of the bleeding tendency of uremia.

Indium-111-antimyosin scintigraphy after doxorubicin therapy in patients with advanced breast cancer Indium-111-antimyosin (111In-antimyosin) scans were performed in 20 women with advanced breast cancer after 10 cycles of chemotherapy consisting of cyclophosphamide, 5-fluorouracil and doxorubicin (total cumulative dose of doxorubicin of 500 mg/m2). Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR). Antimyosin uptake in the myocardium was observed in 17/20 (85%) patients, and HLR after chemotherapy was 1.86 +/- 0.25. Left ventricular ejection fraction (EF) was determined before and after chemotherapy. Patients with decreased EF (8/20, 40%) presented with more intense antimyosin uptake (HLR of 2.11 +/- 0.10 versus 1.70 +/- 0.16 (p = 0.01]. HLR values correlated with EF values after chemotherapy (r = -0.47, p less than 0.05). Positive antimyosin studies after chemotherapy including doxorubicin, indicate the presence of myocardial damage in these patients. Antimyosin studies are a sensitive method to detect myocyte damage in patients after doxorubicin therapy.

Neuroendocrine carcinoma of the ampulla of vater. A case of absence of somatostatin in a vasoactive intestinal polypeptide-, bombesin-, and cholecystokinin-producing tumor. A 31-year-old patient with a clinical picture of obstructive jaundice had surgical treatment, and a primary carcinoid of the ampulla of Vater (VA) was found. The tumor was studied with light microscopy, immunohistochemistry, and electron microscopy. The neoplasm had histopathologic and cytopathologic features similar to those encountered in typical neuroendocrine neoplasms. It is interesting that immunohistochemical techniques disclosed the presence of vasointestinal polypeptide, cholecystokinin, and bombesin; however, unlike most neuroendocrine neoplasms arising in VA, no somatostatin-immunoreactive cells were found.

Prospective evaluation of clinical and pathologic detection of axillary metastases in patients with carcinoma of the breast. Complete axillary dissection was performed in 287 patients undergoing modified radical mastectomy between 1984 and 1987 to identify patterns of axillary node metastases, as well as discontinuous axillary node ("skip") metastases. Positive pathologic findings were compared with preoperative clinical examinations in 266 patients and showed only 60 cases (22.6%) clinically suspicious for tumor, in contrast to 131 (45.6%) with pathologically confirmed positive lymph nodes. Axillary contents were classified level I, II, or III based on their relationship to the pectoralis minor muscle. An average of 24.2 nodes was resected per patient (level I, 10; level II, 8.1; and level III, 5.3). Tumors ranged in size from 0.5 to 12.0 cm (mean, 2.6 cm), and increasing tumor size was associated with an increased likelihood of positive nodes. The data on 204 patients with complete clinical and pathologic data show that of 119 patients with negative level I nodes a limited axillary dissection (level I only) would fail to identify 6 with positive level II and 2 with positive level III nodes, whereas of 85 patients with positive level I nodes limited axillary dissection would fail to identify 17 with positive level II nodes, 7 with positive level III nodes, and 27 with positive levels II and III nodes. Complete axillary dissection (levels I, II, and III) should be performed to stage patients accurately, as well as to remove tumor-involved nodes and diminish local axillary recurrences. Clinical examination of the axilla appears to be a poor means of identifying axillary metastatic cancer.

Value of carvedilol in congestive heart failure secondary to coronary artery disease. Despite considerable interest in the use of beta-blocking agents in congestive heart failure (CHF), their clinical application is limited because of their negative inotropic effects. Beta blockers with vasodilating properties may have the advantage of overcoming this, however. Carvedilol, a beta-blocking agent with vasodilating properties, was evaluated in 17 patients with chronic CHF secondary to ischemic heart disease with a resting left ventricular ejection fraction less than or equal to 45%, who were being maintained on diuretics. Exercise testing, radionuclide ventriculography, and right-sided cardiac catheterization were performed and intraarterial blood pressure measured before and after 8 weeks of carvedilol therapy in a dosage of 12.5 to 50.0 mg twice a day. Twelve patients completed the study and 5 withdrew. Symptomatic and hemodynamic improvement was demonstrated in 11 of the 12 patients. Heart rate and intraarterial blood pressure were both reduced by chronic therapy. Mean +/- standard deviation exercise time improved from 4.3 +/- 1.6 to 7.1 +/- 2.7 minutes (p less than 0.0001), as did resting left ventricular ejection fraction, from 27 +/- 9 to 31 +/- 11% (p less than 0.02). Pulmonary arterial wedge pressure fell from 19 +/- 7 mm Hg to 12 +/- 5 mm Hg (p less than 0.001) and total systemic vascular resistance from 1,752 +/- 403 to 1,497 +/- 310 dynes/s/cm-5/m2 (p less than 0.02). Stroke volume index improved also, from 31 +/- 6 ml to 40 +/- 6 ml (p less than 0.0005). These hemodynamic changes were mediated partly by vasodilation, diminished myocardial oxygen demand and reduction of sympathetic overactivity in the failing heart. These data suggest that carvedilol may have beneficial effects in patients with chronic CHF secondary to coronary artery disease.

Effects of bucindolol on neurohormonal activation in congestive heart failure. To examine the effects of beta-adrenergic blockade on neurohormonal activation in patients with congestive heart failure, 15 men had assessments of hemodynamics and supine peripheral renin and norepinephrine levels before and after 3 months of oral therapy with bucindolol, a nonselective beta antagonist. At baseline, plasma renin activity did not correlate with any hemodynamic parameter. However, norepinephrine levels had a weak correlation with left ventricular end-diastolic pressure (r = 0.74, p less than 0.01), stroke volume index (r = 0.61, p less than 0.02) and pulmonary vascular resistance (r = 0.54, p less than 0.05). Plasma renin decreased with bucindolol therapy, from 11.6 +/- 13.4 to 4.3 +/- 4.1 ng/ml/hour (mean +/- standard deviation; p less than 0.05), whereas plasma norepinephrine was unchanged, from 403 +/- 231 to 408 +/- 217 pg/ml. A wide diversity of the norepinephrine response to bucindolol was observed with reduction of levels in some patients and elevation in others. Although plasma norepinephrine did not decrease, heart rate tended to decrease (from 82 +/- 20 vs 73 +/- 11 min-1, p = 0.059) with beta-adrenergic blockade, suggesting neurohormonal antagonism at the receptor level. No changes in I-123 metaiodobenzylguanidine uptake occurred after bucindolol therapy, suggesting unchanged adrenergic uptake of norepinephrine with beta-blocker therapy. Despite reductions in plasma renin activity and the presence of beta blockade, the response of renin or norepinephrine levels to long-term bucindolol therapy did not predict which patients had improved in hemodynamic status (chi-square = 0.37 for renin, 0.82 for norepinephrine).

Analysis and predictors of pulmonary vascular resistance after cardiac transplantation. Elevated pulmonary vascular resistance is a known risk factor for early death from acute right ventricular failure after orthotopic cardiac transplantation. Patients in whom the elevated pulmonary vascular resistance is due primarily to increased left atrial pressure ("reactive") frequently have normalization of resistance after transplantation, but few studies have detailed the time course and magnitude of these changes. To analyze the response of pulmonary vascular resistance to cardiac transplantation, we analyzed data from 4353 right heart catheterizations on all 182 patients undergoing cardiac transplantation between 1981 and Jan. 1, 1990. Before transplantation 18% of patients had a pulmonary vascular resistance greater than 4 WU, 16% had a pulmonary artery systolic pressure greater than 60 mm Hg, and 16% had a transpulmonary gradient greater than 14 mm Hg. In the overall group of patients, pulmonary vascular resistance (mean value 2.63 WU), transpulmonary gradient (mean value 9.9 mm Hg), and pulmonary artery systolic pressure (mean value 48.0 mm Hg) were normalized within 1 week of cardiac transplantation. In patients with a high preoperative pulmonary vascular resistance (greater than or equal to 4 WU), the resistance fell promptly within 1 week of transplantation but continued to be slightly elevated throughout the period of follow-up. By multiple regression analysis, pulmonary vascular resistance at 1 week and 1 year after transplantation was significantly correlated with the pretransplantation resistance. Pulmonary vascular resistance anytime after transplantation was related to preoperative resistance, body surface area, and pulmonary artery diastolic pressure. Inferences: (1) As a group, cardiac transplant recipients have a normal pulmonary vascular resistance, transpulmonary gradient, and pulmonary artery systolic pressure within 1 week after transplantation with little change thereafter for at least several years. (2) Patients with reversible elevation of pulmonary vascular resistance before cardiac transplantation typically have a reactive and a fixed component. Cardiac transplantation relieves the reactive but not the fixed component. As a result, pulmonary vascular resistance early (within 1 week) and late after transplantation will have fallen but not completely normalized.

Intraoperative pressure profile measurement and continence mechanism adjustment in the Indiana pouch urinary reservoir. We have described herein a simple pressure transducer system which helps the surgeon to tailor suture placement and achieve a continent ileocecal reservoir. It seems that fewer Lembert sutures than previously recommended are necessary to create a continent reservoir, although further study is needed.

Converting enzyme inhibitors and renal function in essential and renovascular hypertension. Converting enzyme inhibitors (CEI) are useful in the treatment of hypertension. However, acute renal deterioration may occur in some conditions in association with the crucial role of angiotensin in the regulation of glomerular filtration rate (GFR), such as volume depletion, severe stenosis of both renal arteries, and stenosis of a single functioning kidney. CEI-induced acute renal failure can develop in the absence of a fall in systemic pressure, is facilitated by prior sodium depletion, and is reversible upon discontinuation of treatment. In a personal study conducted in 28 patients with CEI-induced renal dysfunction (reversible after discontinuation of CEI), the incidence of stenosis of large renal vessels was 61%, whereas 39% of these subjects had no significant renal artery abnormalities. Although the occurrence of such a complication is not a convincingly accurate predictor of the existence of renovascular hypertension, angiographic detection of renal artery stenosis (bilateral or on a single-functioning kidney) may be justified in some of these patients.

Surgical treatment of double major scoliosis. Improvement of the lumbar curve after fusion of the thoracic curve. We have evaluated two methods of surgical treatment of adolescent idiopathic double major scoliosis in 59 patients. In group 1, 31 patients were treated by fusion of the upper curve only. In group 2, 28 patients had lumbar fusions also including most of the lower curve. The magnitude of the lower curve and the correction obtained in traction were good indicators of the correction achieved postoperatively. Forty-four patients were reviewed at a minimum of 10 years after operation. Those in group 1 showed sustained improvement of the lower curve with minimal stiffness and pain. Group 2 patients had lumbar curves of similar severity at review, but had significantly more low back pain and stiffness. The number of lumbar segments which remained mobile appeared to be a critical factor in determining the outcome. Selective fusion of the upper curve in double major scoliosis produces satisfactory results if the lumbar curve is less than 50 degrees. It may also be appropriate for flexible lumbar curves of larger angle.

New primary basal cell carcinomas arising in skin flaps following Mohs micrographic surgery for primary and recurrent basal cell carcinoma. Two patients developed new primary basal cell carcinomas (BCCs) in skin flaps used to reconstruct wounds that followed an earlier primary BCC and a recurrent BCC treated by Mohs micrographic surgery. Criteria for distinguishing a new primary BCC arising in a skin flap or full-thickness skin graft at a previous treatment site for BCC from a truly recurrent BCC are presented. The distinction between a new primary BCC and true tumor recurrence is important for accurate clinical assessment and may have a dramatic impact on the type of subsequent treatment. In addition, there may be less medicolegal liability in the case of a new primary BCC arising at the site of a previously treated BCC than for a BCC that is determined to be recurrent.

Elective resection for diverticular disease of the sigmoid colon. From 1966 to 1987, 177 consecutive patients were operated on electively for diverticular disease of the sigmoid colon. The indications for surgery were: colovesical fistula (n = 12), suspicion of residual abscess (n = 39), two or more previous attacks of acute inflammation (n = 52), chronic symptoms (n = 72) and suspicion of carcinoma (n = 2). An abscess was found at operation in 76 patients (43 per cent) and this was extracolic with local peritonitis in 52 patients (29 per cent). An unsuspected abscess was found in 25 of the 72 patients operated on for chronic symptoms. Colonic resection with primary anastomosis was performed in 95 per cent of the 177 patients and in 94 per cent of those 52 patients with an extracolic abscess. There were no postoperative deaths and no clinical anastomotic leakages. Long-term results were very good in 85 per cent of the 177 patients and in 82 per cent of the 72 patients operated on for chronic symptoms. The results of this series suggest that a one-stage procedure can be safely performed with some technical precautions in most patients operated on electively for diverticular disease, even if an extracolic abscess is found. The good long-term results in patients operated on for chronic symptoms suggest that such symptoms should be taken into account with respect to surgical indications.

Inotropic effects of angiotensin II on human cardiac muscle in vitro. The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure.

Excess deaths from nine chronic diseases in the United States, 1986 To assess excess mortality from chronic disease in the United States, state age-adjusted combined mortality rates for nine chronic diseases in 1986 were compared with three "minimum" rates--two calculated from rates actually achieved in states and a third estimated as the mortality remaining after elimination of one risk factor for each disease. Hawaii had the lowest mortality rate of combined diseases (305/100,000); state excesses ranged from 0% to 37%. The sum of lowest disease-specific rates in any state was 284 per 100,000, indicating excesses of between 7% and 41%. A minimum mortality rate of 224 per 100,000 was estimated to result from elimination of one risk factor for each of the nine diseases, indicating state excesses from 26% to 54%, or 524,000 US deaths. Reduction of US mortality from the nine diseases to the risk factor--eliminated rate is estimated to be associated with an increased life expectancy at birth of 4 years.

Causes, diagnosis, and treatment of pharyngitis. Pharyngitis is a common disease of the respiratory tract that can be caused by several different viruses and bacterial organisms. Clinically speaking, the most important causative agent is group A streptococcus (Streptococcus pyogenes). Although rare, postpharyngitis complications arise as a result of disease caused almost exclusively by group A streptococcus. Because group A streptococcal pharyngitis usually responds well to antimicrobial treatment, it is important to diagnose it. Penicillin, erythromycin, and peroral first-generation cephalosporins have been documented to be effective. In addition to group A streptococcus, C. pneumoniae and M. pneumoniae have also been detected in patients with pharyngitis. The possibility of diagnosing these organisms is limited at the present. Clinical surveys are still needed, moreover, to evaluate the effect of antimicrobial treatment on the disease caused by these organisms. Although routine viral diagnostic methods do not help primary care physicians in treating patients with pharyngitis, information on bacteria and viruses in the immediate environment could prove to be of great help in daily clinical work.

Slow release carbamazepine in treatment of poorly controlled seizures. Thirty three children with poorly controlled epilepsy, and six new patients, were treated with slow release carbamazepine. Twelve of the former had a reduction in the number of seizures of more than half, and 10 had fewer side effects. Three of the new patients stopped having seizures. Variations in plasma concentrations between doses was significantly less when patients took the slow release preparation (22%) compared with the standard preparation (41%). Slow release carbamazepine may improve the conditions of children whose seizures are poorly controlled.

Familial eating epilepsy. Eating-related seizures affecting 20 individuals among 59 siblings belonging to nine families are presented. The type of epilepsy was partial in all the affected individuals, and the seizures complex in 15 and simple in 5, secondarily generalized in the majority. The onset of epilepsy, in most cases, was in the second decade of life. A remarkable degree of intra-family consistency was observed with regard to age at onset, symptomatology of seizures and timing of eating seizures. The study demonstrates sibling clustering in a partial epilepsy, implicating for the first time genetic susceptibility in the aetiology of eating epilepsy.

Placebo controlled trial of xamoterol versus digoxin in chronic atrial fibrillation. Thirteen patients in chronic atrial fibrillation with a normal resting heart rate but with exercise tachycardia and episodes of bradycardia were randomised to treatment periods of two weeks on xamoterol (200 mg twice daily), low dose digoxin, or placebo, in a blind crossover study. The results (mean SEM) of symptom scores, a treadmill exercise test, and 24 hour ambulatory electrocardiographic monitoring were obtained. Xamoterol improved symptom scores and controlled exercise heart rate better than digoxin. Xamoterol was better than digoxin or placebo in reducing the heart rate response to exercise and tended to improve exercise duration. Xamoterol, by reducing the daytime maximum hourly heart rate and increasing the night time minimum hourly heart rate, significantly reduced the difference between the two compared with placebo. In contrast, digoxin tended to reduce both the maximum and minimum hourly heart rates through day and night. Both the frequency and duration of ventricular pauses were reduced by xamoterol but tended to increase with digoxin. Xamoterol reduced both the circadian variation in ventricular response to atrial fibrillation and exercise tachycardia by modulating the heart rate according to the prevailing level of sympathetic activity. These changes were translated into symptomatic benefit for the patients studied.

Results of coronary surgery after failed elective coronary angioplasty in patients with prior coronary surgery The results of coronary artery bypass surgery after failed elective coronary angioplasty in patients who have undergone prior coronary surgery are unknown. Coronary angioplasty may be performed to relieve angina after surgery either to the native coronary vessels or to grafts. Failure of attempted coronary angioplasty may mandate repeat coronary surgery, often in the setting of acute ischemia. From 1980 to 1989, 1,263 patients with prior coronary bypass surgery underwent angioplasty; of these patients, 46 (3.6%) underwent reoperation for failed angioplasty during the same hospital stay. Of the 46 patients who underwent reoperation, 33 had and 13 did not have acute ischemia. In the group with ischemia, 3 patients (9.1%) died and 14 (42.4%) died or had a Q wave myocardial infarction in the hospital compared with no deaths (p = NS) and no deaths or Q wave myocardial infarction (p = 0.005) in the group without ischemia. At 3 years, the actuarial survival rate was 88 +/- 6% in the group with ischemia, whereas there were no deaths in the group without ischemia (p = NS), and freedom from death or myocardial infarction was 51 +/- 10% in the group with ischemia, versus no events in the group without ischemia (p = 0.006). In most patients with prior coronary bypass surgery, coronary angioplasty was performed without the need for repeat coronary bypass surgery. Should coronary angioplasty fail, reoperation in patients without acute ischemia can be performed with overall patient survival comparable to that of elective reoperative coronary bypass without coronary angioplasty.

Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice. Recently, we have established a human squamous cell carcinoma of the maxilla (called MH-85) associated with hypercalcemia, leukocytosis, and cachexia in culture. MH-85 tumor cells caused the same paraneoplastic syndromes in tumor-bearing nude mice. We found that there was a sixfold increase in splenic size in MH-85 tumor-bearing mice. This increase paralleled tumor growth and was reversed by surgical removal of the tumor. Splenectomy in nude mice 1 wk before or 6 wk after tumor inoculation resulted in a decrease in tumor growth, and impairment of hypercalcemia, leukocytosis, and cachexia. In MH-85 tumor-bearing animals that had been pretreated by splenectomy, intravenous injection of fresh normal spleen cells caused an immediate reversal of leukocytosis, hypercalcemia, and cachexia. Since the presence of cachexia in both the patient and the mice carrying the tumor suggested tumor necrosis factor (TNF) may be overproduced, we injected polyclonal neutralizing antibodies raised against murine TNF into tumor-bearing mice. There was a rapid and reproducible decrease in blood ionized calcium, accompanied by suppression of osteoclast activity. No changes in blood ionized calcium were seen in mice injected with normal immune sera. In addition, there was an increase in body weight and decrease in white cell count. Plasma immunoreactive TNF was increased almost fourfold in tumor-bearing nude mice compared with control nude mice. Although TNF activity was undetectable in MH-85 culture supernatants, cells of the macrophage lineage, including spleen cells, released increased amounts of TNF when cultured with MH-85 tumor-conditioned media. These results suggest that splenic cytokines such as TNF may influence the development of the paraneoplastic syndromes of hypercalcemia, leukocytosis, and cachexia in these animals, as well as tumor growth. They also show that paraneoplastic syndromes may be due to factors produced by normal host cells stimulated by the presence of the tumor.

Deep venous thrombosis in intravenous cocaine abuse mimicking septic arthritis of the shoulder. We describe two patients with deep venous thrombosis of the upper extremity who initially were thought to have septic arthritis of the shoulder. These patients had a history of recent intravenous cocaine abuse. The diagnosis of deep venous thrombosis should be considered when a patient with a swollen shoulder has an appropriate history.

Pregnancy outcome in hematologic malignancies. By means of a mail questionnaire, information on a series of 56 pregnancies i in 48 women diagnosed with leukemia or lymphoma was collected from ten hospitals. Seven patients conceived while receiving treatment for their neoplasms; in 22 patients, the hematologic disease was diagnosed during pregnancy, and the remaining 27 patients became pregnant after completion of the antineoplastic treatment. When a comparison was made of the evolution of these pregnancies to that of pregnancies in a healthy population, no increase in the incidence of complications was observed: 64% of the pregnancies went to term, 9% resulted in spontaneous abortion, and 5% resulted in premature births. The observed incidence of one major malformation in 56 pregnancies did not differ from the frequency of malformations in the offspring of healthy individuals. There were no fetal losses in six pregnancies in which conception occurred during the first year after chemotherapy. In spite of the inherent limitations derived from the design of this type of study and the type of subject analyzed, the data here support the hypothesis that the cytostatic treatment of hematologic malignancies, if deemed necessary, should not be postponed because of pregnancy. Moreover, the authors agree with advice recommending that no antifolic or alkylating agents be used for prolonged periods and that radiotherapy be avoided, especially to those fields involving the pelvic area.

Epirubicin at two dose levels with prednisolone as treatment for advanced breast cancer: the results of a randomized trial. Two hundred eleven patients with advanced breast cancer were randomized to receive either epirubicin (E) 50 mg/m2 and prednisolone (LEP) or E 100 mg/m2 and prednisolone (HEP). The intended treatment consisted of 16 courses of LEP or eight courses of HEP given at 3-weekly intervals. Reasons for stopping treatment early included progressive disease, stable disease without symptomatic improvement, or severe toxicity deemed intolerable by either the patient or physician. Toxicity was recorded at 3-weekly and response at 9-weekly intervals using the World Health Organization (WHO) criteria of response and toxicity. Two hundred nine patients were eligible for analysis, 98% of whom have been followed for more than a year. One hundred four patients received LEP and 105 HEP. Significantly worse myelosuppression, alopecia, nausea and vomiting, and mucositis were seen in the high-dose arm (P less than or equal to .001). More patients in the LEP arm stopped treatment before the fourth course than in the HEP arm, and the commonest reason for stopping was progressive disease. A similar median number of courses was given in each arm. There was a significantly higher response in the HEP arm (HEP - complete response [CR] + partial response [PR] = 41%, LEP - CR + PR = 23%). Despite this, no statistically significant differences was seen in overall survival or progression-free interval. The median survival for HEP and LEP was 44 and 46 weeks, respectively.

Four and a half year follow up of women with dyskaryotic cervical smears. OBJECTIVE--To determine the proportion of women with mild or moderate dyskaryosis in cervical smears who (a) progress to cervical intraepithelial neoplasia grade III or worse or (b) regress. DESIGN--Four and a half year cytological follow up study of women with mild or moderate dyskaryosis in cervical smears. SETTING--666 Women (mean age 28 (SD 8) years; range 14-74) found to have borderline, mild, or moderate dyskaryosis on routine screening. RESULTS--45 Women (6.8%) had a cone biopsy recommended on the basis of an abnormal follow up smear (severe dyskaryosis suggestive of cervical intraepithelial neoplasia grade III or invasive cancer), and in one patient cervical intraepithelial neoplasia grade III was reported in a biopsy specimen after dilatation and curettage. Life table analysis gave a 14% probability of a patient being recommended for a biopsy after four and a half years of follow up (95% confidence interval 12% to 15%). There was a significant excess incidence of invasive cancer of the cervix in the series compared with the general population (five cases observed compared with less than 0.1 expected). 157 Patients (24%) showed reversion to a normal cell pattern sustained in several smears over more than 18 months but a single negative smear was an unreliable indicator of apparent regression. Having two successive smears showing mild dyskaryosis or a smear at any time showing moderate dyskaryosis was a significant predictor of a subsequent severely dyskaryotic smear. CONCLUSIONS--Women found to have mild or moderate dyskaryosis in cervical smears should be kept under regular surveillance. The optimum management of these patients--by cytology or colposcopy--needs to be determined by randomised controlled trials.

Safety of the transbronchial biopsy in outpatients. The objective of our study was to determine the safety of transbronchial biopsy (TBB) in nonhospitalized patients. The design was a prospective study of the consecutive cases from July 1987 until September 1988 in the setting of a university hospital of the third level with 1,800 beds. The patients were a consecutive sample of 169 patients who had 184 procedures of fiberoptic bronchoscopy (FOB) with TBB performed. They suffered from different diseases: lung nodules or masses, diffuse interstitial disease, alveolar condensation, etc. An FOB with TBB was performed in immunocompetent outpatients, who were kept under observation for four hours and then had a chest roentgenogram taken afterwards. We contacted them again after 72 hours to rule out delayed complications. In three cases, more than 100 ml of blood were obtained during the FOB, without significant hemoptysis being recorded in those patients during the observation period; chest pain occurred in 15 patients during the TBB; pneumothorax occurred in two patients (1 percent), one of whom required admission to the hospital, without requiring chest tube drainage. Other complications are reported (bronchospasm, parenchymal hemorrhage, and pneumonia). In conclusion, we consider the TBB to be a technique with a low incidence of complications for outpatients, so therefore we do not believe that admission to the hospital is mandatory for this type of patient, although we do recommend a longer observation period.

Interictal spikes and hippocampal somatostatin levels in temporal lobe epilepsy. We investigated the relationship between somatostatin-like immunoreactivity (SSLI) and interictal spikes (IIS) in human temporal lobe epileptic tissue. IIS counted manually from depth electrode recordings obtained preoperatively were expressed as spike frequency in anterior, middle, and posterior portions of hippocampus. SSLI was determined by radioimmunoassay (RIA). An inverse relationship between SSLI in the entorhinal cortex (EC) and IIS frequency in hippocampus was present (r = -0.55, p = 0.06). No correlation between IIS and SSLI in CA4, CA3, CA1, or the dentate was evident. This finding suggests a role of the EC in generation, regulation, or expression of interictal paroxysmal electrical activity in temporal lobe epilepsy (TLE), for which somatostatin may be a marker.

Recurrent thoracic outlet syndrome after first rib resection. Seventy-seven patients with 84 operated limbs participated in a follow-up examination on an average of about six years after the resection of the first rib for thoracic outlet syndrome (TOS). Forty-two limbs (50%) were totally asymptomatic one month after the operation and remained so for at least half a year postoperatively. In the follow-up examination, 31 limbs were still asymptomatic, whereas 11 limbs had the same symptoms as before the operation. Of the nine patients with recurrent TOS (two with bilateral resection), seven were women and two were men. These nine patients were on average 38 years old (range = 19 to 51 years) and their jobs consisted of monotonous desk work. Seven of 11 stumps of the first rib were subluxated disclosed by the cervical rotation-lateral-flexion test. The occurrence of a subluxated stump of the first rib in the group of asymptomatic patients was far lower, only 3% (p less than .001). Of the 42 patients with persistent problems, a subluxated stump was encountered in seven (17%). Results of this follow-up examination suggest that monotonous desk work is an important factor causing kinesiologic abnormalities in the thoracic aperture. This abnormal kinesiology contributes to the recurrence of TOS symptoms even after the resection of the first rib.